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Entry
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- *608072 - NHL REPEAT-CONTAINING PROTEIN 1; NHLRC1
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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">*608072</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/608072">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000187566;t=ENST00000340650" 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=378884" 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=608072" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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<div 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=ENSG00000187566;t=ENST00000340650" 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_198586" 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_198586" 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=608072" 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=06995&isoform_id=06995_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/NHLRC1" 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/33469244,38176278,40255283,50400890,74355125,74355594,74355596,119575796" 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/Q6VVB1" 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=378884" 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=ENSG00000187566;t=ENST00000340650" 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=NHLRC1" 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=NHLRC1" 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+378884" 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/NHLRC1" 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:378884" 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/378884" 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=chr6&hgg_gene=ENST00000340650.6&hgg_start=18120440&hgg_end=18122677&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:21576" 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/nhlrc1" 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=608072[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=608072[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000187566" 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=NHLRC1" 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=NHLRC1" 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=NHLRC1" 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=NHLRC1&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/PA134916338" 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:21576" 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:2145264" 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/NHLRC1#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:2145264" 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/378884/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA000690/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=378884" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00189955;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:378884" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=NHLRC1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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608072
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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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NHL REPEAT-CONTAINING PROTEIN 1; NHLRC1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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EPM2B GENE; EPM2B<br />
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MALIN
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=NHLRC1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">NHLRC1</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
|
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<strong>
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<em>
|
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Cytogenetic location: <a href="/geneMap/6/96?start=-3&limit=10&highlight=96">6p22.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:18120440-18122677&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'})">6:18,120,440-18,122,677</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>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
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<th>
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Phenotype
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</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">
|
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<a href="/geneMap/6/96?start=-3&limit=10&highlight=96">
|
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6p22.3
|
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</a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Myoclonic epilepsy of Lafora 2
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
|
<a href="/entry/620681"> 620681 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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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|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/608072" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/608072" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</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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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
|
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</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>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
|
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<strong>Description</strong>
|
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</span>
|
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>The NHLRC1 gene encodes malin, a single subunit E3 ubiquitin (UBB; <a href="/entry/191339">191339</a>) ligase, which contains a RING-HC-type zinc finger and 6 NHL domains and is subclassified as a member of the RING-HCa family (<a href="#6" class="mim-tip-reference" title="Gentry, M. S., Worby, C. A., Dixon, J. E. <strong>Insights into Lafora disease: malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin.</strong> Proc. Nat. Acad. Sci. 102: 8501-8506, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15930137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15930137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15930137[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0503285102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15930137">Gentry et al., 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15930137" 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>Within an 840-kb region on chromosome 6p22.3 in which the putative EPM2B locus for Lafora disease (<a href="/entry/620681">620681</a>) was mapped, <a href="#1" class="mim-tip-reference" title="Chan, E. M., Young, E. J., Ianzano, L., Munteanu, I., Zhao, X., Christopoulos, C. C., Avanzini, G., Elia, M., Ackerley, C. A., Jovic, N. J., Bohlega, S., Andermann, E., Rouleau, G. A., Delgado-Escueta, A. V., Minassian, B. A., Scherer, S. W. <strong>Mutations in NHLRC1 cause progressive myoclonus epilepsy.</strong> Nature Genet. 35: 125-127, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12958597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12958597</a>] [<a href="https://doi.org/10.1038/ng1238" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12958597">Chan et al. (2003)</a> identified a single-exon gene, termed NHLRC1. The gene is predicted to encode a 395-amino acid protein, termed malin ('mal' for seizure in French), containing a zinc finger of the RING type and 6 NHL-repeat protein-protein interaction domains. The presence of the RING finger predicts an E3 ubiquitin ligase function. Northern blot analysis indicated 2 transcripts of 1.5 kb and 2.4 kb in all tissues examined, including multiple subregions of the brain. In cultured cells, malin was localized at the endoplasmic reticulum and, to a lesser extent, in the nucleus. These results were similar to those observed for laforin (EPM2A; <a href="/entry/607566">607566</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12958597" 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="#1" class="mim-tip-reference" title="Chan, E. M., Young, E. J., Ianzano, L., Munteanu, I., Zhao, X., Christopoulos, C. C., Avanzini, G., Elia, M., Ackerley, C. A., Jovic, N. J., Bohlega, S., Andermann, E., Rouleau, G. A., Delgado-Escueta, A. V., Minassian, B. A., Scherer, S. W. <strong>Mutations in NHLRC1 cause progressive myoclonus epilepsy.</strong> Nature Genet. 35: 125-127, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12958597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12958597</a>] [<a href="https://doi.org/10.1038/ng1238" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12958597">Chan et al. (2003)</a> identified the NHLRC1 gene between markers D6S1688 and D6S1567 on chromosome 6p22.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12958597" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By yeast 2-hybrid screen of a human brain cDNA library, <a href="#6" class="mim-tip-reference" title="Gentry, M. S., Worby, C. A., Dixon, J. E. <strong>Insights into Lafora disease: malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin.</strong> Proc. Nat. Acad. Sci. 102: 8501-8506, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15930137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15930137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15930137[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0503285102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15930137">Gentry et al. (2005)</a> found that malin directly bound and interacted with laforin in HEK293T cells in vivo. Laforin is polyubiquitinated in a malin-dependent manner, which leads to laforin degradation. Ubiquitination depended on malin's RING domain but not on its NHL domains, whereas the NHL domains functioned as a substrate-interacting motif to bind laforin. Mutations in the NHLRC1 gene abolished both laforin polyubiquitination and degradation. <a href="#6" class="mim-tip-reference" title="Gentry, M. S., Worby, C. A., Dixon, J. E. <strong>Insights into Lafora disease: malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin.</strong> Proc. Nat. Acad. Sci. 102: 8501-8506, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15930137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15930137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15930137[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0503285102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15930137">Gentry et al. (2005)</a> concluded that malin is a single-subunit E3 ligase, that laforin is a malin substrate, and that malin regulates laforin protein concentration. They further suggested that mutations in the NHLRC1 gene resulting in loss of the E3 ligase activity of malin underlie the onset of Lafora disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15930137" 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="Lohi, H., Ianzano, L., Zhao, X.-C., Chan, E. M., Turnbull, J., Scherer, S. W., Ackerley, C. A., Minassian, B. A. <strong>Novel glycogen synthase kinase 3 and ubiquitination pathways in progressive myoclonus epilepsy.</strong> Hum. Molec. Genet. 14: 2727-2736, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16115820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16115820</a>] [<a href="https://doi.org/10.1093/hmg/ddi306" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16115820">Lohi et al. (2005)</a> showed that laforin is a GSK3B (<a href="/entry/605004">605004</a>) ser9 phosphatase, and therefore capable of inactivating glycogen synthase (GYS1; <a href="/entry/138570">138570</a>) through GSK3. Laforin also interacted with malin, which has been shown to bind GYS1. The authors proposed that laforin, in response to appearance of polyglucosans, directs 2 negative feedback pathways: polyglucosan-laforin-GSK3-GYS1 to inhibit GYS1 activity and polyglucosan-laforin-malin-GYS1 to remove GYS1 through proteasomal degradation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16115820" 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>Cori disease (<a href="/entry/232400">232400</a>) is a glycogen storage disease characterized by deficiency of the glycogen debranching enzyme AGL (<a href="/entry/610860">610860</a>). <a href="#2" class="mim-tip-reference" title="Cheng, A., Zhang, M., Gentry, M. S., Worby, C. A., Dixon, J. E., Saltiel, A. R. <strong>A role for AGL ubiquitination in the glycogen storage disorders of Lafora and Cori's disease.</strong> Genes Dev. 21: 2399-2409, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17908927/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17908927</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17908927[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/10.1101/gad.1553207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17908927">Cheng et al. (2007)</a> showed that malin interacted with mouse Agl and promoted its ubiquitination. Transfection studies in HepG2 cells showed that Agl was cytoplasmic, whereas malin was predominantly nuclear. However, after depletion of glycogen stores, about 90% of transfected cells exhibited partial nuclear Agl staining. Elevation of cAMP increased malin levels and malin/Agl complex formation. <a href="#2" class="mim-tip-reference" title="Cheng, A., Zhang, M., Gentry, M. S., Worby, C. A., Dixon, J. E., Saltiel, A. R. <strong>A role for AGL ubiquitination in the glycogen storage disorders of Lafora and Cori's disease.</strong> Genes Dev. 21: 2399-2409, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17908927/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17908927</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17908927[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/10.1101/gad.1553207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17908927">Cheng et al. (2007)</a> concluded that ubiquitination of AGL may play a role in the pathophysiology of both Lafora disease and Cori disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17908927" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Mittal, S., Dubey, D., Yamakawa, K., Ganesh, S. <strong>Lafora disease proteins malin and laforin are recruited to aggresomes in response to proteasomal impairment.</strong> Hum. Molec. Genet. 16: 753-762, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17337485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17337485</a>] [<a href="https://doi.org/10.1093/hmg/ddm006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17337485">Mittal et al. (2007)</a> showed that laforin and malin were recruited to aggresomes upon proteasomal blockade, possibly to clear misfolded proteins through the ubiquitin-proteasome system (UPS). <a href="#5" class="mim-tip-reference" title="Garyali, P., Siwach, P., Singh, P. K., Puri, R., Mittal, S., Sengupta, S., Parihar, R., Ganesh, S. <strong>The malin-laforin complex suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system.</strong> Hum. Molec. Genet. 18: 688-700, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19036738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19036738</a>] [<a href="https://doi.org/10.1093/hmg/ddn398" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19036738">Garyali et al. (2009)</a> tested this possibility using a variety of cytotoxic misfolded proteins, including the expanded polyglutamine protein, as potential substrates. Laforin and malin, together with Hsp70 (HSPA1A; <a href="/entry/140550">140550</a>) as a functional complex, suppressed the cellular toxicity of misfolded proteins; all 3 members of the complex were required for this function. Laforin and malin interacted with misfolded proteins and promoted their degradation through the UPS, and they were recruited to the polyglutamine aggregates and reduced the frequency of aggregate-positive cells. <a href="#5" class="mim-tip-reference" title="Garyali, P., Siwach, P., Singh, P. K., Puri, R., Mittal, S., Sengupta, S., Parihar, R., Ganesh, S. <strong>The malin-laforin complex suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system.</strong> Hum. Molec. Genet. 18: 688-700, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19036738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19036738</a>] [<a href="https://doi.org/10.1093/hmg/ddn398" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19036738">Garyali et al. (2009)</a> suggested that the malin-laforin complex is a novel player in the neuronal response to misfolded proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17337485+19036738" 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 34 probands with myoclonic epilepsy of Lafora, <a href="#1" class="mim-tip-reference" title="Chan, E. M., Young, E. J., Ianzano, L., Munteanu, I., Zhao, X., Christopoulos, C. C., Avanzini, G., Elia, M., Ackerley, C. A., Jovic, N. J., Bohlega, S., Andermann, E., Rouleau, G. A., Delgado-Escueta, A. V., Minassian, B. A., Scherer, S. W. <strong>Mutations in NHLRC1 cause progressive myoclonus epilepsy.</strong> Nature Genet. 35: 125-127, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12958597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12958597</a>] [<a href="https://doi.org/10.1038/ng1238" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12958597">Chan et al. (2003)</a> identified 17 different mutations in the NHLRC1 gene in 26 families (see MELF2, EPM2B; <a href="/entry/620681">620681</a>), including 8 deletions, 1 insertion, 7 missense changes, and 1 nonsense change (see, e.g., <a href="#0001">608072.0001</a>). Eighteen families were homozygous and 8 were compound heterozygous for the mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12958597" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Gomez-Abad, C., Gomez-Garre, P., Gutierrez-Delicado, E., Saygi, S., Michelucci, R., Tassinari, C. A., Rodriguez de Cordoba, S., Serratosa, J. M. <strong>Lafora disease due to EPM2B mutations: a clinical and genetic study.</strong> Neurology 64: 982-986, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781812</a>] [<a href="https://doi.org/10.1212/01.WNL.0000154519.10805.F7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15781812">Gomez-Abad et al. (2005)</a> identified 18 mutations, including 12 novel mutations, in the malin gene (see, e.g., <a href="#0005">608072.0005</a>-<a href="#0007">608072.0007</a>) in 23 of 25 patients with Lafora disease who did not have mutations in the laforin gene. P69A (<a href="#0002">608072.0002</a>) was the predominant mutation, identified in 14 chromosomes from 9 unrelated patients; haplotype analysis suggested a founder effect for only 2 of these families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15781812" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Singh, S., Suzuki, T., Uchiyama, A., Kumada, S., Moriyama, N., Hirose, S., Takahashi, Y., Sugie, H., Mizoguchi, K., Inoue, Y., Kimura, K., Sawaishi, Y., Yamakawa, K., Ganesh, S. <strong>Mutations in the NHLRC1 gene are the common cause for Lafora disease in the Japanese population.</strong> J. Hum. Genet. 50: 347-352, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16021330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16021330</a>] [<a href="https://doi.org/10.1007/s10038-005-0263-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16021330">Singh et al. (2005)</a> identified 6 different mutations in the NHLRC1 gene in 5 of 8 Japanese families with Lafora disease. Another Japanese family had a mutation in the EPM2A gene, and 2 Japanese families did not have mutations in either gene. <a href="#13" class="mim-tip-reference" title="Singh, S., Suzuki, T., Uchiyama, A., Kumada, S., Moriyama, N., Hirose, S., Takahashi, Y., Sugie, H., Mizoguchi, K., Inoue, Y., Kimura, K., Sawaishi, Y., Yamakawa, K., Ganesh, S. <strong>Mutations in the NHLRC1 gene are the common cause for Lafora disease in the Japanese population.</strong> J. Hum. Genet. 50: 347-352, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16021330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16021330</a>] [<a href="https://doi.org/10.1007/s10038-005-0263-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16021330">Singh et al. (2005)</a> concluded that mutations in the NHLRC1 gene are a common cause of Lafora disease in Japan. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16021330" 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="#12" class="mim-tip-reference" title="Singh, S., Sethi, I., Francheschetti, S., Riggio, C., Avanzini, G., Yamakawa, K., Delgado-Escueta, A. V., Ganesh, S. <strong>Novel NHLRC1 mutations and genotype-phenotype correlations in patients with Lafora's progressive myoclonic epilepsy.</strong> J. Med. Genet. 43: e48, 2006. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16950819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16950819</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16950819[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmg.2005.039479" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16950819">Singh et al. (2006)</a> identified 7 different mutations, including 2 novel mutations, in the NHLRC1 gene in affected members of 8 families with Lafora disease. The authors stated that 39 different mutations had been identified in the NHLRC1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16950819" 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="Ianzano, L., Zhang, J., Chan, E. M., Zhao, X.-C., Lohi, H., Scherer, S. W., Minassian, B. A. <strong>Lafora progressive myoclonus epilepsy mutation database-EPM2A and NHLRC1 (EMP2B) genes.</strong> Hum. Mutat. 26: 397 only, 2005. Note: Full article online.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16134145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16134145</a>] [<a href="https://doi.org/10.1002/humu.9376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16134145">Ianzano et al. (2005)</a> reported the creation of a Lafora progressive myoclonus epilepsy mutation database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16134145" 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>More than 5% of purebred miniature wirehaired dachshunds (MWHDs) in the United Kingdom suffer an autosomal recessive progressive myoclonic epilepsy (PME), which <a href="#10" class="mim-tip-reference" title="Lohi, H., Young, E. J., Fitzmaurice, S. N., Rusbridge, C., Chan, E. M., Vervoort, M., Turnbull, J., Zhao, X.-C., Ianzano, L., Paterson, A. D., Sutter, N. B., Ostrander, E. A., Andre, C., Shelton, G. D., Ackerley, C. A., Scherer, S. W., Minassian, B. A. <strong>Expanded repeat in canine epilepsy.</strong> Science 307: 81 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15637270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15637270</a>] [<a href="https://doi.org/10.1126/science.1102832" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15637270">Lohi et al. (2005)</a> showed to be Lafora disease (<a href="/entry/620681">620681</a>). Using homozygosity and linkage analysis, they mapped the MWHD disease locus to canine chromosome 35, which is syntenic in its entirety to human 6p25-p21. They then cloned canine Epm2b (NHLRC1). PCR identified a repeat region in affected dogs and revealed biallelic expansion of the dodecamer repeat with 19 to 26 copies of the D sequence. Comparing the amount of Epm2b mRNA in skeletal muscle from 3 affected dogs and 2 controls with quantitative RT-PCR showed that affected mRNA levels were more than 900 times reduced. To determine whether the extra D sequence is specific to MWHDs, <a href="#10" class="mim-tip-reference" title="Lohi, H., Young, E. J., Fitzmaurice, S. N., Rusbridge, C., Chan, E. M., Vervoort, M., Turnbull, J., Zhao, X.-C., Ianzano, L., Paterson, A. D., Sutter, N. B., Ostrander, E. A., Andre, C., Shelton, G. D., Ackerley, C. A., Scherer, S. W., Minassian, B. A. <strong>Expanded repeat in canine epilepsy.</strong> Science 307: 81 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15637270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15637270</a>] [<a href="https://doi.org/10.1126/science.1102832" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15637270">Lohi et al. (2005)</a> sequenced Epm2b from 2 normal unrelated dogs from each of 128 breeds. Sixty percent of their chromosomes had 3 repeats (2 Ds and 1 T) and 40%, 2 repeats (1 D and 1 T). Almost all breeds had examples of both variants in homozygous or heterozygous state. They tested the next non-MWHD PME case to present to the clinic, a basset hound, and found a homozygous 14-copy expansion of the repeat. <a href="#10" class="mim-tip-reference" title="Lohi, H., Young, E. J., Fitzmaurice, S. N., Rusbridge, C., Chan, E. M., Vervoort, M., Turnbull, J., Zhao, X.-C., Ianzano, L., Paterson, A. D., Sutter, N. B., Ostrander, E. A., Andre, C., Shelton, G. D., Ackerley, C. A., Scherer, S. W., Minassian, B. A. <strong>Expanded repeat in canine epilepsy.</strong> Science 307: 81 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15637270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15637270</a>] [<a href="https://doi.org/10.1126/science.1102832" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15637270">Lohi et al. (2005)</a> devised a test to detect and counteract the mutant allele through controlled breeding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15637270" 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="#3" class="mim-tip-reference" title="Criado, O., Aguado, C., Gayarre, J., Duran-Trio, L., Garcia-Cabrero, A. M., Mouron, S., Juana-Lopez, L., Dominguez, M., Navarro, C., Serratosa, J. M., Sanchez, M., Sanz, P., Bovolenta, P., Knecht, E., Rodriguez de Cordoba, S. <strong>Lafora bodies and neurological defects in malin-deficient mice correlate with impaired autophagy.</strong> Hum. Molec. Genet. 21: 1521-1533, 2012. Note: Erratum: Hum. Molec. Genet. 21: 4366 only, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22186026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22186026</a>] [<a href="https://doi.org/10.1093/hmg/ddr590" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22186026">Criado et al. (2012)</a> found that Epm2b -/- mice bred normally but showed accumulation of Lafora bodies (LBs), characteristic of Lafora disease. LBs were not detected in tissues from wildtype mice at any age or in tissues from Epm2b -/- mice at postnatal day-16 (P16), but LBs were abundant in brain, heart, and skeletal muscle in Epm2b -/- mice at 3 months of age and increased progressively with time. Epm2b -/- mice also showed accumulation of laforin in brain. At P16, when no LBs were detected, laforin was mostly present in the soluble fraction of all examined tissues. Laforin was increasingly found in the insoluble fraction as Epm2b -/- mice aged. Laforin colocalized with ubiquitin and glycogen synthase at 2 distinct polyglucosan structures and accumulated in these structures. Epm2b -/- mice also exhibited compromised autophagy that was independent of activation of the Mtor (<a href="/entry/601231">601231</a>) pathway. Epm2b -/- mice also displayed neurologic and behavioral abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22186026" 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="DePaoli-Roach, A. A., Segvich, D. M., Meyer, C. M., Rahimi, Y., Worby, C. A., Gentry, M. S., Roach, P. J. <strong>Laforin and malin knockout mice have normal glucose disposal and insulin sensitivity.</strong> Hum. Molec. Genet. 21: 1604-1610, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22186021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22186021</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22186021[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/ddr598" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22186021">DePaoli-Roach et al. (2012)</a> found that Epm2b -/- mice had normal glucose disposal, insulin sensitivity, and cardiac function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22186021" 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> rs28940575 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28940575;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/rs28940575?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=rs28940575" 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=rs28940575" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 4 French Canadian families with myoclonic epilepsy of Lafora-2 (MELF2; <a href="/entry/620681">620681</a>), <a href="#1" class="mim-tip-reference" title="Chan, E. M., Young, E. J., Ianzano, L., Munteanu, I., Zhao, X., Christopoulos, C. C., Avanzini, G., Elia, M., Ackerley, C. A., Jovic, N. J., Bohlega, S., Andermann, E., Rouleau, G. A., Delgado-Escueta, A. V., Minassian, B. A., Scherer, S. W. <strong>Mutations in NHLRC1 cause progressive myoclonus epilepsy.</strong> Nature Genet. 35: 125-127, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12958597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12958597</a>] [<a href="https://doi.org/10.1038/ng1238" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12958597">Chan et al. (2003)</a> identified a homozygous 76T-A change in the NHLRC1 gene, resulting in a cys26-to-ser (C26S) substitution in one of the 7 conserved cysteine residues critical for the zinc-binding ability of the RING finger. Haplotype analysis indicated a founder effect. <a href="#12" class="mim-tip-reference" title="Singh, S., Sethi, I., Francheschetti, S., Riggio, C., Avanzini, G., Yamakawa, K., Delgado-Escueta, A. V., Ganesh, S. <strong>Novel NHLRC1 mutations and genotype-phenotype correlations in patients with Lafora's progressive myoclonic epilepsy.</strong> J. Med. Genet. 43: e48, 2006. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16950819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16950819</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16950819[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmg.2005.039479" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16950819">Singh et al. (2006)</a> devised a DNA-based diagnostic test to specifically screen for the C26S mutation in patients with Lafora disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12958597+16950819" 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> rs28940576 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28940576;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/rs28940576?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=rs28940576" 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=rs28940576" 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=RCV000002705 OR RCV000188208 OR RCV000192026 OR RCV003952338" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002705, RCV000188208, RCV000192026, RCV003952338" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002705...</a>
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<p>In 3 families with myoclonic epilepsy of Lafora-2 (MELF2; <a href="/entry/620681">620681</a>), <a href="#1" class="mim-tip-reference" title="Chan, E. M., Young, E. J., Ianzano, L., Munteanu, I., Zhao, X., Christopoulos, C. C., Avanzini, G., Elia, M., Ackerley, C. A., Jovic, N. J., Bohlega, S., Andermann, E., Rouleau, G. A., Delgado-Escueta, A. V., Minassian, B. A., Scherer, S. W. <strong>Mutations in NHLRC1 cause progressive myoclonus epilepsy.</strong> Nature Genet. 35: 125-127, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12958597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12958597</a>] [<a href="https://doi.org/10.1038/ng1238" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12958597">Chan et al. (2003)</a> identified a homozygous 205C-G change in the NHLRC1 gene, resulting in a pro69-to-ala (P69A) substitution. Four additional affected families had the P69A mutation in compound heterozygosity with another mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12958597" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Gomez-Abad, C., Gomez-Garre, P., Gutierrez-Delicado, E., Saygi, S., Michelucci, R., Tassinari, C. A., Rodriguez de Cordoba, S., Serratosa, J. M. <strong>Lafora disease due to EPM2B mutations: a clinical and genetic study.</strong> Neurology 64: 982-986, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781812</a>] [<a href="https://doi.org/10.1212/01.WNL.0000154519.10805.F7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15781812">Gomez-Abad et al. (2005)</a> identified the P69A mutation in 14 chromosomes from 9 unrelated patients with Lafora disease; haplotype analysis suggested a founder effect for only 2 of these families. One patient who was homozygous for the mutation presented with hepatic failure and did not develop neurologic symptoms. The P69A mutation is located in the zinc RING finger domain of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15781812" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 MYOCLONIC EPILEPSY OF LAFORA 2</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs587776542 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776542;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/rs587776542?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=rs587776542" 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=rs587776542" 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=RCV000002706 OR RCV000188221 OR RCV000192029 OR RCV002326660" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002706, RCV000188221, RCV000192029, RCV002326660" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002706...</a>
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<p>In 2 families with myoclonic epilepsy of Lafora-2 (MELF2; <a href="/entry/620681">620681</a>), <a href="#1" class="mim-tip-reference" title="Chan, E. M., Young, E. J., Ianzano, L., Munteanu, I., Zhao, X., Christopoulos, C. C., Avanzini, G., Elia, M., Ackerley, C. A., Jovic, N. J., Bohlega, S., Andermann, E., Rouleau, G. A., Delgado-Escueta, A. V., Minassian, B. A., Scherer, S. W. <strong>Mutations in NHLRC1 cause progressive myoclonus epilepsy.</strong> Nature Genet. 35: 125-127, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12958597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12958597</a>] [<a href="https://doi.org/10.1038/ng1238" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12958597">Chan et al. (2003)</a> identified a homozygous 2-bp deletion, 468_469AG, in the NHLRC1 gene. Two additional families had the deletion in compound heterozygosity with a 1-bp deletion (<a href="#0004">608072.0004</a>), and 1 family had the deletion in compound heterozygosity with the P69A mutation (<a href="#0002">608072.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12958597" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 MYOCLONIC EPILEPSY OF LAFORA 2</strong>
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NHLRC1, 1-BP DEL, 990G
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776543 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776543;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=rs587776543" 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=rs587776543" 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=RCV000002707" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002707" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002707</a>
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<p>In a family with myoclonic epilepsy of Lafora-2 (MELF2; <a href="/entry/620681">620681</a>), <a href="#1" class="mim-tip-reference" title="Chan, E. M., Young, E. J., Ianzano, L., Munteanu, I., Zhao, X., Christopoulos, C. C., Avanzini, G., Elia, M., Ackerley, C. A., Jovic, N. J., Bohlega, S., Andermann, E., Rouleau, G. A., Delgado-Escueta, A. V., Minassian, B. A., Scherer, S. W. <strong>Mutations in NHLRC1 cause progressive myoclonus epilepsy.</strong> Nature Genet. 35: 125-127, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12958597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12958597</a>] [<a href="https://doi.org/10.1038/ng1238" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12958597">Chan et al. (2003)</a> identified a homozygous 1-bp deletion, 990G, in the NHLRC1 gene. Two other affected families had compound heterozygosity for the 1-bp deletion and the 468AG deletion (<a href="#0003">608072.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12958597" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 MYOCLONIC EPILEPSY OF LAFORA 2</strong>
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NHLRC1, ARG265TER
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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> rs121917875 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121917875;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/rs121917875?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=rs121917875" 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=rs121917875" 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=RCV000002708" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002708" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002708</a>
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<p>In a Turkish patient with myoclonic epilepsy of Lafora-2 (MELF2; <a href="/entry/620681">620681</a>), <a href="#7" class="mim-tip-reference" title="Gomez-Abad, C., Gomez-Garre, P., Gutierrez-Delicado, E., Saygi, S., Michelucci, R., Tassinari, C. A., Rodriguez de Cordoba, S., Serratosa, J. M. <strong>Lafora disease due to EPM2B mutations: a clinical and genetic study.</strong> Neurology 64: 982-986, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781812</a>] [<a href="https://doi.org/10.1212/01.WNL.0000154519.10805.F7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15781812">Gomez-Abad et al. (2005)</a> identified a homozygous 793C-T transition in the NHLRC1 gene, resulting in an arg265-to-ter (R265X) substitution. The patient presented at age 13 years with myoclonic seizures. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15781812" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<strong>.0006 MYOCLONIC EPILEPSY OF LAFORA 2</strong>
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NHLRC1, ILE198ASN
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121917876 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121917876;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=rs121917876" 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=rs121917876" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002709 OR RCV000192028 OR RCV001818119" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002709, RCV000192028, RCV001818119" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002709...</a>
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<p>In 2 affected members of a family from Ecuador with myclonic epilepsy of Lafora-2 (MELF2; <a href="/entry/620681">620681</a>), <a href="#7" class="mim-tip-reference" title="Gomez-Abad, C., Gomez-Garre, P., Gutierrez-Delicado, E., Saygi, S., Michelucci, R., Tassinari, C. A., Rodriguez de Cordoba, S., Serratosa, J. M. <strong>Lafora disease due to EPM2B mutations: a clinical and genetic study.</strong> Neurology 64: 982-986, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781812</a>] [<a href="https://doi.org/10.1212/01.WNL.0000154519.10805.F7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15781812">Gomez-Abad et al. (2005)</a> identified a homozygous 593T-A transversion in the NHLRC1 gene, resulting in an ile198-to-asn (I198N) substitution in an NHL protein-protein interaction domain. Both patients presented with partial seizures with secondary generalization at ages 5 and 14, respectively. The patient with onset at age 5 years also developed cognitive decline and was unable to attend school. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15781812" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<strong>.0007 MYOCLONIC EPILEPSY OF LAFORA 2</strong>
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NHLRC1, ASP308ALA
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852859 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852859;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=rs137852859" 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=rs137852859" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002710" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002710" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002710</a>
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<span class="mim-text-font">
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<p>In an Italian patient with myoclonic epilepsy of Lafora-2 (MELF2; <a href="/entry/620681">620681</a>), <a href="#7" class="mim-tip-reference" title="Gomez-Abad, C., Gomez-Garre, P., Gutierrez-Delicado, E., Saygi, S., Michelucci, R., Tassinari, C. A., Rodriguez de Cordoba, S., Serratosa, J. M. <strong>Lafora disease due to EPM2B mutations: a clinical and genetic study.</strong> Neurology 64: 982-986, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781812</a>] [<a href="https://doi.org/10.1212/01.WNL.0000154519.10805.F7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15781812">Gomez-Abad et al. (2005)</a> identified a homozygous 923A-T transversion in the NHLRC1 gene, resulting in an asp308-to-ala (D308A) substitution. The patient presented at age 16 years with myoclonic and absence seizures and developed cognitive decline at age 18 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15781812" 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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|
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|
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|
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<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Chan2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chan, E. M., Young, E. J., Ianzano, L., Munteanu, I., Zhao, X., Christopoulos, C. C., Avanzini, G., Elia, M., Ackerley, C. A., Jovic, N. J., Bohlega, S., Andermann, E., Rouleau, G. A., Delgado-Escueta, A. V., Minassian, B. A., Scherer, S. W.
|
|
<strong>Mutations in NHLRC1 cause progressive myoclonus epilepsy.</strong>
|
|
Nature Genet. 35: 125-127, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12958597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12958597</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12958597" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng1238" target="_blank">Full Text</a>]
|
|
|
|
|
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</p>
|
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</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Cheng2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cheng, A., Zhang, M., Gentry, M. S., Worby, C. A., Dixon, J. E., Saltiel, A. R.
|
|
<strong>A role for AGL ubiquitination in the glycogen storage disorders of Lafora and Cori's disease.</strong>
|
|
Genes Dev. 21: 2399-2409, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17908927/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17908927</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17908927[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=17908927" 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/10.1101/gad.1553207" target="_blank">Full Text</a>]
|
|
|
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|
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</p>
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Criado2012" class="mim-anchor"></a>
|
|
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|
|
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|
|
Criado, O., Aguado, C., Gayarre, J., Duran-Trio, L., Garcia-Cabrero, A. M., Mouron, S., Juana-Lopez, L., Dominguez, M., Navarro, C., Serratosa, J. M., Sanchez, M., Sanz, P., Bovolenta, P., Knecht, E., Rodriguez de Cordoba, S.
|
|
<strong>Lafora bodies and neurological defects in malin-deficient mice correlate with impaired autophagy.</strong>
|
|
Hum. Molec. Genet. 21: 1521-1533, 2012. Note: Erratum: Hum. Molec. Genet. 21: 4366 only, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22186026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22186026</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22186026" 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/ddr590" target="_blank">Full Text</a>]
|
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</p>
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</li>
|
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|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="DePaoli-Roach2012" class="mim-anchor"></a>
|
|
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|
|
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|
|
DePaoli-Roach, A. A., Segvich, D. M., Meyer, C. M., Rahimi, Y., Worby, C. A., Gentry, M. S., Roach, P. J.
|
|
<strong>Laforin and malin knockout mice have normal glucose disposal and insulin sensitivity.</strong>
|
|
Hum. Molec. Genet. 21: 1604-1610, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22186021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22186021</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22186021[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=22186021" 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/ddr598" target="_blank">Full Text</a>]
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|
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|
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Garyali, P., Siwach, P., Singh, P. K., Puri, R., Mittal, S., Sengupta, S., Parihar, R., Ganesh, S.
|
|
<strong>The malin-laforin complex suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system.</strong>
|
|
Hum. Molec. Genet. 18: 688-700, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19036738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19036738</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19036738" 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/ddn398" target="_blank">Full Text</a>]
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|
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|
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|
|
<li>
|
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<a id="Gentry2005" class="mim-anchor"></a>
|
|
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|
|
<p class="mim-text-font">
|
|
Gentry, M. S., Worby, C. A., Dixon, J. E.
|
|
<strong>Insights into Lafora disease: malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 8501-8506, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15930137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15930137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15930137[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=15930137" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
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|
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[<a href="https://doi.org/10.1073/pnas.0503285102" target="_blank">Full Text</a>]
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<div class="">
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Gomez-Abad, C., Gomez-Garre, P., Gutierrez-Delicado, E., Saygi, S., Michelucci, R., Tassinari, C. A., Rodriguez de Cordoba, S., Serratosa, J. M.
|
|
<strong>Lafora disease due to EPM2B mutations: a clinical and genetic study.</strong>
|
|
Neurology 64: 982-986, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781812</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15781812" 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.0000154519.10805.F7" target="_blank">Full Text</a>]
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|
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|
|
|
|
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|
|
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|
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<a id="Ianzano2005" class="mim-anchor"></a>
|
|
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|
|
<p class="mim-text-font">
|
|
Ianzano, L., Zhang, J., Chan, E. M., Zhao, X.-C., Lohi, H., Scherer, S. W., Minassian, B. A.
|
|
<strong>Lafora progressive myoclonus epilepsy mutation database-EPM2A and NHLRC1 (EMP2B) genes.</strong>
|
|
Hum. Mutat. 26: 397 only, 2005. Note: Full article online.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16134145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16134145</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16134145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.9376" target="_blank">Full Text</a>]
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|
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|
|
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|
|
|
|
<li>
|
|
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|
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<a id="Lohi2005" class="mim-anchor"></a>
|
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<div class="">
|
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|
|
Lohi, H., Ianzano, L., Zhao, X.-C., Chan, E. M., Turnbull, J., Scherer, S. W., Ackerley, C. A., Minassian, B. A.
|
|
<strong>Novel glycogen synthase kinase 3 and ubiquitination pathways in progressive myoclonus epilepsy.</strong>
|
|
Hum. Molec. Genet. 14: 2727-2736, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16115820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16115820</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16115820" 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/ddi306" target="_blank">Full Text</a>]
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|
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|
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<a id="Lohi2005" class="mim-anchor"></a>
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Lohi, H., Young, E. J., Fitzmaurice, S. N., Rusbridge, C., Chan, E. M., Vervoort, M., Turnbull, J., Zhao, X.-C., Ianzano, L., Paterson, A. D., Sutter, N. B., Ostrander, E. A., Andre, C., Shelton, G. D., Ackerley, C. A., Scherer, S. W., Minassian, B. A.
|
|
<strong>Expanded repeat in canine epilepsy.</strong>
|
|
Science 307: 81 only, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15637270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15637270</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15637270" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1102832" target="_blank">Full Text</a>]
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<a id="Mittal2007" class="mim-anchor"></a>
|
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|
|
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|
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Mittal, S., Dubey, D., Yamakawa, K., Ganesh, S.
|
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<strong>Lafora disease proteins malin and laforin are recruited to aggresomes in response to proteasomal impairment.</strong>
|
|
Hum. Molec. Genet. 16: 753-762, 2007.
|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17337485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17337485</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17337485" 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/ddm006" target="_blank">Full Text</a>]
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<a id="Singh2006" class="mim-anchor"></a>
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Singh, S., Sethi, I., Francheschetti, S., Riggio, C., Avanzini, G., Yamakawa, K., Delgado-Escueta, A. V., Ganesh, S.
|
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<strong>Novel NHLRC1 mutations and genotype-phenotype correlations in patients with Lafora's progressive myoclonic epilepsy.</strong>
|
|
J. Med. Genet. 43: e48, 2006. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16950819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16950819</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16950819[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=16950819" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.2005.039479" target="_blank">Full Text</a>]
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<a id="Singh2005" class="mim-anchor"></a>
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Singh, S., Suzuki, T., Uchiyama, A., Kumada, S., Moriyama, N., Hirose, S., Takahashi, Y., Sugie, H., Mizoguchi, K., Inoue, Y., Kimura, K., Sawaishi, Y., Yamakawa, K., Ganesh, S.
|
|
<strong>Mutations in the NHLRC1 gene are the common cause for Lafora disease in the Japanese population.</strong>
|
|
J. Hum. Genet. 50: 347-352, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16021330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16021330</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16021330" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10038-005-0263-7" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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Bao Lige - updated : 05/12/2022
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<span class="mim-text-font">
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George E. Tiller - updated : 8/10/2009<br>George E. Tiller - updated : 12/10/2008<br>Patricia A. Hartz - updated : 11/2/2007<br>Cassandra L. Kniffin - updated : 2/15/2007<br>Cassandra L. Kniffin - updated : 11/7/2005<br>Cassandra L. Kniffin - updated : 6/9/2005<br>Victor A. McKusick - updated : 12/29/2003
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<a id="creationDate" class="mim-anchor"></a>
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<span class="text-nowrap mim-text-font">
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin : 9/3/2003
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 01/25/2024
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<span class="mim-text-font">
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carol : 01/24/2024<br>carol : 01/21/2023<br>mgross : 05/12/2022<br>carol : 01/09/2019<br>mcolton : 01/20/2015<br>carol : 3/6/2014<br>carol : 2/20/2014<br>wwang : 8/20/2009<br>terry : 8/10/2009<br>wwang : 12/10/2008<br>mgross : 11/2/2007<br>wwang : 2/20/2007<br>ckniffin : 2/15/2007<br>wwang : 5/4/2006<br>wwang : 11/17/2005<br>ckniffin : 11/7/2005<br>wwang : 6/14/2005<br>ckniffin : 6/9/2005<br>wwang : 2/3/2005<br>wwang : 2/1/2005<br>tkritzer : 1/15/2004<br>terry : 12/29/2003<br>alopez : 10/16/2003<br>carol : 9/12/2003<br>ckniffin : 9/11/2003<br>ckniffin : 9/11/2003
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<span class="mim-font">
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<strong>*</strong> 608072
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<h3>
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<span class="mim-font">
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NHL REPEAT-CONTAINING PROTEIN 1; NHLRC1
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<span class="mim-font">
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EPM2B GENE; EPM2B<br />
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MALIN
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: NHLRC1</em></strong>
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</span>
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<strong>
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<em>
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Cytogenetic location: 6p22.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 6:18,120,440-18,122,677 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
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6p22.3
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<span class="mim-font">
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Myoclonic epilepsy of Lafora 2
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</td>
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<span class="mim-font">
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620681
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<span class="mim-font">
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Autosomal recessive
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<span class="mim-font">
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3
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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<span class="mim-text-font">
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<p>The NHLRC1 gene encodes malin, a single subunit E3 ubiquitin (UBB; 191339) ligase, which contains a RING-HC-type zinc finger and 6 NHL domains and is subclassified as a member of the RING-HCa family (Gentry et al., 2005). </p>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</h4>
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<span class="mim-text-font">
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<p>Within an 840-kb region on chromosome 6p22.3 in which the putative EPM2B locus for Lafora disease (620681) was mapped, Chan et al. (2003) identified a single-exon gene, termed NHLRC1. The gene is predicted to encode a 395-amino acid protein, termed malin ('mal' for seizure in French), containing a zinc finger of the RING type and 6 NHL-repeat protein-protein interaction domains. The presence of the RING finger predicts an E3 ubiquitin ligase function. Northern blot analysis indicated 2 transcripts of 1.5 kb and 2.4 kb in all tissues examined, including multiple subregions of the brain. In cultured cells, malin was localized at the endoplasmic reticulum and, to a lesser extent, in the nucleus. These results were similar to those observed for laforin (EPM2A; 607566). </p>
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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>Chan et al. (2003) identified the NHLRC1 gene between markers D6S1688 and D6S1567 on chromosome 6p22.3. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By yeast 2-hybrid screen of a human brain cDNA library, Gentry et al. (2005) found that malin directly bound and interacted with laforin in HEK293T cells in vivo. Laforin is polyubiquitinated in a malin-dependent manner, which leads to laforin degradation. Ubiquitination depended on malin's RING domain but not on its NHL domains, whereas the NHL domains functioned as a substrate-interacting motif to bind laforin. Mutations in the NHLRC1 gene abolished both laforin polyubiquitination and degradation. Gentry et al. (2005) concluded that malin is a single-subunit E3 ligase, that laforin is a malin substrate, and that malin regulates laforin protein concentration. They further suggested that mutations in the NHLRC1 gene resulting in loss of the E3 ligase activity of malin underlie the onset of Lafora disease. </p><p>Lohi et al. (2005) showed that laforin is a GSK3B (605004) ser9 phosphatase, and therefore capable of inactivating glycogen synthase (GYS1; 138570) through GSK3. Laforin also interacted with malin, which has been shown to bind GYS1. The authors proposed that laforin, in response to appearance of polyglucosans, directs 2 negative feedback pathways: polyglucosan-laforin-GSK3-GYS1 to inhibit GYS1 activity and polyglucosan-laforin-malin-GYS1 to remove GYS1 through proteasomal degradation. </p><p>Cori disease (232400) is a glycogen storage disease characterized by deficiency of the glycogen debranching enzyme AGL (610860). Cheng et al. (2007) showed that malin interacted with mouse Agl and promoted its ubiquitination. Transfection studies in HepG2 cells showed that Agl was cytoplasmic, whereas malin was predominantly nuclear. However, after depletion of glycogen stores, about 90% of transfected cells exhibited partial nuclear Agl staining. Elevation of cAMP increased malin levels and malin/Agl complex formation. Cheng et al. (2007) concluded that ubiquitination of AGL may play a role in the pathophysiology of both Lafora disease and Cori disease. </p><p>Mittal et al. (2007) showed that laforin and malin were recruited to aggresomes upon proteasomal blockade, possibly to clear misfolded proteins through the ubiquitin-proteasome system (UPS). Garyali et al. (2009) tested this possibility using a variety of cytotoxic misfolded proteins, including the expanded polyglutamine protein, as potential substrates. Laforin and malin, together with Hsp70 (HSPA1A; 140550) as a functional complex, suppressed the cellular toxicity of misfolded proteins; all 3 members of the complex were required for this function. Laforin and malin interacted with misfolded proteins and promoted their degradation through the UPS, and they were recruited to the polyglutamine aggregates and reduced the frequency of aggregate-positive cells. Garyali et al. (2009) suggested that the malin-laforin complex is a novel player in the neuronal response to misfolded proteins. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In 34 probands with myoclonic epilepsy of Lafora, Chan et al. (2003) identified 17 different mutations in the NHLRC1 gene in 26 families (see MELF2, EPM2B; 620681), including 8 deletions, 1 insertion, 7 missense changes, and 1 nonsense change (see, e.g., 608072.0001). Eighteen families were homozygous and 8 were compound heterozygous for the mutations. </p><p>Gomez-Abad et al. (2005) identified 18 mutations, including 12 novel mutations, in the malin gene (see, e.g., 608072.0005-608072.0007) in 23 of 25 patients with Lafora disease who did not have mutations in the laforin gene. P69A (608072.0002) was the predominant mutation, identified in 14 chromosomes from 9 unrelated patients; haplotype analysis suggested a founder effect for only 2 of these families. </p><p>Singh et al. (2005) identified 6 different mutations in the NHLRC1 gene in 5 of 8 Japanese families with Lafora disease. Another Japanese family had a mutation in the EPM2A gene, and 2 Japanese families did not have mutations in either gene. Singh et al. (2005) concluded that mutations in the NHLRC1 gene are a common cause of Lafora disease in Japan. </p><p>Singh et al. (2006) identified 7 different mutations, including 2 novel mutations, in the NHLRC1 gene in affected members of 8 families with Lafora disease. The authors stated that 39 different mutations had been identified in the NHLRC1 gene. </p><p>Ianzano et al. (2005) reported the creation of a Lafora progressive myoclonus epilepsy mutation database. </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>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>More than 5% of purebred miniature wirehaired dachshunds (MWHDs) in the United Kingdom suffer an autosomal recessive progressive myoclonic epilepsy (PME), which Lohi et al. (2005) showed to be Lafora disease (620681). Using homozygosity and linkage analysis, they mapped the MWHD disease locus to canine chromosome 35, which is syntenic in its entirety to human 6p25-p21. They then cloned canine Epm2b (NHLRC1). PCR identified a repeat region in affected dogs and revealed biallelic expansion of the dodecamer repeat with 19 to 26 copies of the D sequence. Comparing the amount of Epm2b mRNA in skeletal muscle from 3 affected dogs and 2 controls with quantitative RT-PCR showed that affected mRNA levels were more than 900 times reduced. To determine whether the extra D sequence is specific to MWHDs, Lohi et al. (2005) sequenced Epm2b from 2 normal unrelated dogs from each of 128 breeds. Sixty percent of their chromosomes had 3 repeats (2 Ds and 1 T) and 40%, 2 repeats (1 D and 1 T). Almost all breeds had examples of both variants in homozygous or heterozygous state. They tested the next non-MWHD PME case to present to the clinic, a basset hound, and found a homozygous 14-copy expansion of the repeat. Lohi et al. (2005) devised a test to detect and counteract the mutant allele through controlled breeding. </p><p>Criado et al. (2012) found that Epm2b -/- mice bred normally but showed accumulation of Lafora bodies (LBs), characteristic of Lafora disease. LBs were not detected in tissues from wildtype mice at any age or in tissues from Epm2b -/- mice at postnatal day-16 (P16), but LBs were abundant in brain, heart, and skeletal muscle in Epm2b -/- mice at 3 months of age and increased progressively with time. Epm2b -/- mice also showed accumulation of laforin in brain. At P16, when no LBs were detected, laforin was mostly present in the soluble fraction of all examined tissues. Laforin was increasingly found in the insoluble fraction as Epm2b -/- mice aged. Laforin colocalized with ubiquitin and glycogen synthase at 2 distinct polyglucosan structures and accumulated in these structures. Epm2b -/- mice also exhibited compromised autophagy that was independent of activation of the Mtor (601231) pathway. Epm2b -/- mice also displayed neurologic and behavioral abnormalities. </p><p>DePaoli-Roach et al. (2012) found that Epm2b -/- mice had normal glucose disposal, insulin sensitivity, and cardiac function. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>7 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 MYOCLONIC EPILEPSY OF LAFORA 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NHLRC1, CYS26SER
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<br />
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SNP: rs28940575,
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gnomAD: rs28940575,
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ClinVar: RCV000002704, RCV000192025, RCV000483691
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 4 French Canadian families with myoclonic epilepsy of Lafora-2 (MELF2; 620681), Chan et al. (2003) identified a homozygous 76T-A change in the NHLRC1 gene, resulting in a cys26-to-ser (C26S) substitution in one of the 7 conserved cysteine residues critical for the zinc-binding ability of the RING finger. Haplotype analysis indicated a founder effect. Singh et al. (2006) devised a DNA-based diagnostic test to specifically screen for the C26S mutation in patients with Lafora disease. </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>.0002 MYOCLONIC EPILEPSY OF LAFORA 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NHLRC1, PRO69ALA
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<br />
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SNP: rs28940576,
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gnomAD: rs28940576,
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ClinVar: RCV000002705, RCV000188208, RCV000192026, RCV003952338
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 families with myoclonic epilepsy of Lafora-2 (MELF2; 620681), Chan et al. (2003) identified a homozygous 205C-G change in the NHLRC1 gene, resulting in a pro69-to-ala (P69A) substitution. Four additional affected families had the P69A mutation in compound heterozygosity with another mutation. </p><p>Gomez-Abad et al. (2005) identified the P69A mutation in 14 chromosomes from 9 unrelated patients with Lafora disease; haplotype analysis suggested a founder effect for only 2 of these families. One patient who was homozygous for the mutation presented with hepatic failure and did not develop neurologic symptoms. The P69A mutation is located in the zinc RING finger domain 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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<h4>
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<span class="mim-font">
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<strong>.0003 MYOCLONIC EPILEPSY OF LAFORA 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NHLRC1, 2-BP DEL, 468AG
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<br />
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SNP: rs587776542,
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gnomAD: rs587776542,
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ClinVar: RCV000002706, RCV000188221, RCV000192029, RCV002326660
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 families with myoclonic epilepsy of Lafora-2 (MELF2; 620681), Chan et al. (2003) identified a homozygous 2-bp deletion, 468_469AG, in the NHLRC1 gene. Two additional families had the deletion in compound heterozygosity with a 1-bp deletion (608072.0004), and 1 family had the deletion in compound heterozygosity with the P69A mutation (608072.0002). </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 MYOCLONIC EPILEPSY OF LAFORA 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NHLRC1, 1-BP DEL, 990G
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<br />
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SNP: rs587776543,
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ClinVar: RCV000002707
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a family with myoclonic epilepsy of Lafora-2 (MELF2; 620681), Chan et al. (2003) identified a homozygous 1-bp deletion, 990G, in the NHLRC1 gene. Two other affected families had compound heterozygosity for the 1-bp deletion and the 468AG deletion (608072.0003). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 MYOCLONIC EPILEPSY OF LAFORA 2</strong>
|
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</span>
|
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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NHLRC1, ARG265TER
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<br />
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SNP: rs121917875,
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gnomAD: rs121917875,
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ClinVar: RCV000002708
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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 Turkish patient with myoclonic epilepsy of Lafora-2 (MELF2; 620681), Gomez-Abad et al. (2005) identified a homozygous 793C-T transition in the NHLRC1 gene, resulting in an arg265-to-ter (R265X) substitution. The patient presented at age 13 years with myoclonic seizures. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0006 MYOCLONIC EPILEPSY OF LAFORA 2</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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NHLRC1, ILE198ASN
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<br />
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SNP: rs121917876,
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ClinVar: RCV000002709, RCV000192028, RCV001818119
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In 2 affected members of a family from Ecuador with myclonic epilepsy of Lafora-2 (MELF2; 620681), Gomez-Abad et al. (2005) identified a homozygous 593T-A transversion in the NHLRC1 gene, resulting in an ile198-to-asn (I198N) substitution in an NHL protein-protein interaction domain. Both patients presented with partial seizures with secondary generalization at ages 5 and 14, respectively. The patient with onset at age 5 years also developed cognitive decline and was unable to attend school. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0007 MYOCLONIC EPILEPSY OF LAFORA 2</strong>
|
|
</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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NHLRC1, ASP308ALA
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<br />
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SNP: rs137852859,
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ClinVar: RCV000002710
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
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<p>In an Italian patient with myoclonic epilepsy of Lafora-2 (MELF2; 620681), Gomez-Abad et al. (2005) identified a homozygous 923A-T transversion in the NHLRC1 gene, resulting in an asp308-to-ala (D308A) substitution. The patient presented at age 16 years with myoclonic and absence seizures and developed cognitive decline at age 18 years. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
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<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chan, E. M., Young, E. J., Ianzano, L., Munteanu, I., Zhao, X., Christopoulos, C. C., Avanzini, G., Elia, M., Ackerley, C. A., Jovic, N. J., Bohlega, S., Andermann, E., Rouleau, G. A., Delgado-Escueta, A. V., Minassian, B. A., Scherer, S. W.
|
|
<strong>Mutations in NHLRC1 cause progressive myoclonus epilepsy.</strong>
|
|
Nature Genet. 35: 125-127, 2003.
|
|
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|
|
[PubMed: 12958597]
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[Full Text: https://doi.org/10.1038/ng1238]
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</p>
|
|
</li>
|
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Cheng, A., Zhang, M., Gentry, M. S., Worby, C. A., Dixon, J. E., Saltiel, A. R.
|
|
<strong>A role for AGL ubiquitination in the glycogen storage disorders of Lafora and Cori's disease.</strong>
|
|
Genes Dev. 21: 2399-2409, 2007.
|
|
|
|
|
|
[PubMed: 17908927]
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[Full Text: https://doi.org/10.1101/gad.1553207]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Criado, O., Aguado, C., Gayarre, J., Duran-Trio, L., Garcia-Cabrero, A. M., Mouron, S., Juana-Lopez, L., Dominguez, M., Navarro, C., Serratosa, J. M., Sanchez, M., Sanz, P., Bovolenta, P., Knecht, E., Rodriguez de Cordoba, S.
|
|
<strong>Lafora bodies and neurological defects in malin-deficient mice correlate with impaired autophagy.</strong>
|
|
Hum. Molec. Genet. 21: 1521-1533, 2012. Note: Erratum: Hum. Molec. Genet. 21: 4366 only, 2012.
|
|
|
|
|
|
[PubMed: 22186026]
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|
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddr590]
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
DePaoli-Roach, A. A., Segvich, D. M., Meyer, C. M., Rahimi, Y., Worby, C. A., Gentry, M. S., Roach, P. J.
|
|
<strong>Laforin and malin knockout mice have normal glucose disposal and insulin sensitivity.</strong>
|
|
Hum. Molec. Genet. 21: 1604-1610, 2012.
|
|
|
|
|
|
[PubMed: 22186021]
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|
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[Full Text: https://doi.org/10.1093/hmg/ddr598]
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|
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Garyali, P., Siwach, P., Singh, P. K., Puri, R., Mittal, S., Sengupta, S., Parihar, R., Ganesh, S.
|
|
<strong>The malin-laforin complex suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system.</strong>
|
|
Hum. Molec. Genet. 18: 688-700, 2009.
|
|
|
|
|
|
[PubMed: 19036738]
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|
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddn398]
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gentry, M. S., Worby, C. A., Dixon, J. E.
|
|
<strong>Insights into Lafora disease: malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 8501-8506, 2005.
|
|
|
|
|
|
[PubMed: 15930137]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0503285102]
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gomez-Abad, C., Gomez-Garre, P., Gutierrez-Delicado, E., Saygi, S., Michelucci, R., Tassinari, C. A., Rodriguez de Cordoba, S., Serratosa, J. M.
|
|
<strong>Lafora disease due to EPM2B mutations: a clinical and genetic study.</strong>
|
|
Neurology 64: 982-986, 2005.
|
|
|
|
|
|
[PubMed: 15781812]
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|
|
[Full Text: https://doi.org/10.1212/01.WNL.0000154519.10805.F7]
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|
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Ianzano, L., Zhang, J., Chan, E. M., Zhao, X.-C., Lohi, H., Scherer, S. W., Minassian, B. A.
|
|
<strong>Lafora progressive myoclonus epilepsy mutation database-EPM2A and NHLRC1 (EMP2B) genes.</strong>
|
|
Hum. Mutat. 26: 397 only, 2005. Note: Full article online.
|
|
|
|
|
|
[PubMed: 16134145]
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|
|
[Full Text: https://doi.org/10.1002/humu.9376]
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lohi, H., Ianzano, L., Zhao, X.-C., Chan, E. M., Turnbull, J., Scherer, S. W., Ackerley, C. A., Minassian, B. A.
|
|
<strong>Novel glycogen synthase kinase 3 and ubiquitination pathways in progressive myoclonus epilepsy.</strong>
|
|
Hum. Molec. Genet. 14: 2727-2736, 2005.
|
|
|
|
|
|
[PubMed: 16115820]
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|
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[Full Text: https://doi.org/10.1093/hmg/ddi306]
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</p>
|
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</li>
|
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|
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<li>
|
|
<p class="mim-text-font">
|
|
Lohi, H., Young, E. J., Fitzmaurice, S. N., Rusbridge, C., Chan, E. M., Vervoort, M., Turnbull, J., Zhao, X.-C., Ianzano, L., Paterson, A. D., Sutter, N. B., Ostrander, E. A., Andre, C., Shelton, G. D., Ackerley, C. A., Scherer, S. W., Minassian, B. A.
|
|
<strong>Expanded repeat in canine epilepsy.</strong>
|
|
Science 307: 81 only, 2005.
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|
|
[PubMed: 15637270]
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|
|
[Full Text: https://doi.org/10.1126/science.1102832]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Mittal, S., Dubey, D., Yamakawa, K., Ganesh, S.
|
|
<strong>Lafora disease proteins malin and laforin are recruited to aggresomes in response to proteasomal impairment.</strong>
|
|
Hum. Molec. Genet. 16: 753-762, 2007.
|
|
|
|
|
|
[PubMed: 17337485]
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddm006]
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|
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</p>
|
|
</li>
|
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<li>
|
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<p class="mim-text-font">
|
|
Singh, S., Sethi, I., Francheschetti, S., Riggio, C., Avanzini, G., Yamakawa, K., Delgado-Escueta, A. V., Ganesh, S.
|
|
<strong>Novel NHLRC1 mutations and genotype-phenotype correlations in patients with Lafora's progressive myoclonic epilepsy.</strong>
|
|
J. Med. Genet. 43: e48, 2006. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 16950819]
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|
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|
|
[Full Text: https://doi.org/10.1136/jmg.2005.039479]
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|
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Singh, S., Suzuki, T., Uchiyama, A., Kumada, S., Moriyama, N., Hirose, S., Takahashi, Y., Sugie, H., Mizoguchi, K., Inoue, Y., Kimura, K., Sawaishi, Y., Yamakawa, K., Ganesh, S.
|
|
<strong>Mutations in the NHLRC1 gene are the common cause for Lafora disease in the Japanese population.</strong>
|
|
J. Hum. Genet. 50: 347-352, 2005.
|
|
|
|
|
|
[PubMed: 16021330]
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|
|
[Full Text: https://doi.org/10.1007/s10038-005-0263-7]
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</p>
|
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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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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
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<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
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</span>
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</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Bao Lige - updated : 05/12/2022<br>George E. Tiller - updated : 8/10/2009<br>George E. Tiller - updated : 12/10/2008<br>Patricia A. Hartz - updated : 11/2/2007<br>Cassandra L. Kniffin - updated : 2/15/2007<br>Cassandra L. Kniffin - updated : 11/7/2005<br>Cassandra L. Kniffin - updated : 6/9/2005<br>Victor A. McKusick - updated : 12/29/2003
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</span>
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</div>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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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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Cassandra L. Kniffin : 9/3/2003
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</span>
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</div>
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<span class="text-nowrap mim-text-font">
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Edit History:
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<span class="mim-text-font">
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carol : 01/25/2024<br>carol : 01/24/2024<br>carol : 01/21/2023<br>mgross : 05/12/2022<br>carol : 01/09/2019<br>mcolton : 01/20/2015<br>carol : 3/6/2014<br>carol : 2/20/2014<br>wwang : 8/20/2009<br>terry : 8/10/2009<br>wwang : 12/10/2008<br>mgross : 11/2/2007<br>wwang : 2/20/2007<br>ckniffin : 2/15/2007<br>wwang : 5/4/2006<br>wwang : 11/17/2005<br>ckniffin : 11/7/2005<br>wwang : 6/14/2005<br>ckniffin : 6/9/2005<br>wwang : 2/3/2005<br>wwang : 2/1/2005<br>tkritzer : 1/15/2004<br>terry : 12/29/2003<br>alopez : 10/16/2003<br>carol : 9/12/2003<br>ckniffin : 9/11/2003<br>ckniffin : 9/11/2003
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