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Entry
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- #620681 - MYOCLONIC EPILEPSY OF LAFORA 2; MELF2
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- OMIM
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<p>
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<span class="h4">#620681</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<li role="presentation">
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<a href="/clinicalSynopsis/620681"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS254800,PS254780"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#diagnosis">Diagnosis</a>
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<a href="#mapping">Mapping</a>
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<a href="#inheritance">Inheritance</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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<li role="presentation" style="margin-left: 1em">
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<a href="#populationGenetics">Population Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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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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</a>
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</h4>
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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=" 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 in 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://clinicaltrials.gov/search?cond=MYOCLONIC EPILEPSY OF LAFORA" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1389/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=620681[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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<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://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>
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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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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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620681
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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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|
|
MYOCLONIC EPILEPSY OF LAFORA 2; MELF2
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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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EPILEPSY, PROGRESSIVE MYOCLONIC, 2B; EPM2B<br />
|
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LAFORA DISEASE 2
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
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</span>
|
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed 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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<th>
|
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Gene/Locus
|
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</th>
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<th>
|
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Gene/Locus <br /> MIM number
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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>
|
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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">
|
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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>
|
|
</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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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</td>
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<td>
|
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<span class="mim-font">
|
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NHLRC1
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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/608072"> 608072 </a>
|
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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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<a href="/clinicalSynopsis/620681" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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<div class="btn-group">
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<a href="/phenotypicSeries/PS254800,PS254780" class="btn btn-info" role="button"> Phenotypic Series </a>
|
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/620681" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/620681" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
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<p />
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small" style="margin: 5px">
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> INHERITANCE </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> HEAD & NECK </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Eyes </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Loss of vision <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246635007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246635007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7973008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7973008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H54.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H54.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/369.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">369.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3665346&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3665346</a>, <a href="https://bioportal.bioontology.org/search?q=C3665386&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3665386</a>, <a href="https://bioportal.bioontology.org/search?q=C0042798&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042798</a>, <a href="https://bioportal.bioontology.org/search?q=C0456909&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0456909</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000618" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000618</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000572" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000572</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000505</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000572" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000572</a>]</span><br /> -
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Photosensitivity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/90128006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">90128006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349506&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349506</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000992" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000992</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000992" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000992</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
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<strong> NEUROLOGIC </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
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<em> Central Nervous System </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
|
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<span class="mim-font">
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|
- Myoclonic epilepsy, progressive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267581004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267581004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0751778&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0751778</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002123" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002123</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002123" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002123</a>]</span><br /> -
|
|
Generalized tonic-clonic seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1217136003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1217136003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G40.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G40.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0494475&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0494475</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002069" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002069</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0025190" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0025190</a>]</span><br /> -
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|
Absence seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/79631006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">79631006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4316903&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4316903</a>, <a href="https://bioportal.bioontology.org/search?q=C0014553&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0014553</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002121" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002121</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002121" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002121</a>]</span><br /> -
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|
Myoclonus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/17450006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">17450006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G25.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G25.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/333.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">333.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027066&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027066</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001336" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001336</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001336" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001336</a>]</span><br /> -
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|
Mental deterioration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234985&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234985</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001268" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001268</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001268" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001268</a>]</span><br /> -
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Dementia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/52448006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">52448006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12348006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12348006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F03.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F03.90</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F03" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F03</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/290.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">290.1</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/294.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">294.2</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">290</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011265&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011265</a>, <a href="https://bioportal.bioontology.org/search?q=C0497327&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0497327</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000726" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000726</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000726" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000726</a>]</span><br /> -
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|
Ataxia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20262006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20262006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/39384006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">39384006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85102008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85102008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R27.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R27.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.84</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0004134&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0004134</a>, <a href="https://bioportal.bioontology.org/search?q=C1135207&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1135207</a>, <a href="https://bioportal.bioontology.org/search?q=C0007758&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007758</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0010867" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010867</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span><br /> -
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Loss of ambulation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836843&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836843</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002505</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002505</a>]</span><br /> -
|
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Neurologic deterioration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854838&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854838</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002344" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002344</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002344" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002344</a>]</span><br /> -
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Intracellular PAS-positive polyglucosan inclusion bodies ('Lafora' bodies) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850769&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850769</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> LABORATORY ABNORMALITIES </strong>
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</span>
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</div>
|
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Intracellular PAS-positive polyglucosan inclusion bodies ('Lafora' bodies) can be found in various tissues (brain, liver, muscle, heart, skin) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850771&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850771</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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|
</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
|
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<span class="mim-font">
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|
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- Onset in late childhood/adolescence<br /> -
|
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Progressive disorder <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864985&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864985</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003676" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003676</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003676" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003676</a>]</span><br /> -
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|
Survival after disease onset 5-15 years (in most cases)<br />
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</span>
|
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</div>
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</div>
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
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</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
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<div>
|
|
<span class="mim-font">
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|
|
- Caused by mutation in the NHL repeat-containing 1 gene (NHLRC1, <a href="/entry/608072#0001">608072.0001</a>)<br />
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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 class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
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|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
|
|
|
|
|
|
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|
|
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|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Myoclonic epilepsy of Lafora
|
|
- <a href="/phenotypicSeries/PS254780">PS254780</a>
|
|
- 2 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/6/96?start=-3&limit=10&highlight=96"> 6p22.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/620681"> Myoclonic epilepsy of Lafora 2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/620681"> 620681 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608072"> NHLRC1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608072"> 608072 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/6/925?start=-3&limit=10&highlight=925"> 6q24.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/254780"> Myoclonic epilepsy of Lafora 1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/254780"> 254780 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607566"> EPM2A </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607566"> 607566 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Epilepsy, progressive myoclonic
|
|
- <a href="/phenotypicSeries/PS254800">PS254800</a>
|
|
- 13 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/4/340?start=-3&limit=10&highlight=340"> 4q21.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/254900"> Epilepsy, progressive myoclonic 4, with or without renal failure </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/254900"> 254900 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602257"> SCARB2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602257"> 602257 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/4/357?start=-3&limit=10&highlight=357"> 4q21.21 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616640"> ?Epilepsy, progressive myoclonic, 10 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616640"> 616640 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616639"> PRDM8 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616639"> 616639 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/6/96?start=-3&limit=10&highlight=96"> 6p22.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/620681"> Myoclonic epilepsy of Lafora 2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/620681"> 620681 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608072"> NHLRC1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608072"> 608072 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/6/925?start=-3&limit=10&highlight=925"> 6q24.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/254780"> Myoclonic epilepsy of Lafora 1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/254780"> 254780 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607566"> EPM2A </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607566"> 607566 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/7/301?start=-3&limit=10&highlight=301"> 7q11.21 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611726"> Epilepsy, progressive myoclonic 3, with or without intracellular inclusions </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611726"> 611726 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611725"> KCTD7 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611725"> 611725 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/11/213?start=-3&limit=10&highlight=213"> 11p15.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616187"> Epilepsy, progressive myoclonic 7 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
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<a href="/entry/619191"> Epilepsy, progressive myoclonic, 12 </a>
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<a href="/entry/254800"> Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) </a>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<p>A number sign (#) is used with this entry because myoclonic epilepsy of Lafora-2 (MELF2), also known as progressive myoclonic epilepsy-2B (EPM2B), is caused by homozygous or compound heterozygous mutation in the NHLRC1 gene (<a href="/entry/608072">608072</a>), which encodes malin, on chromosome 6p22.</p>
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<p>The Lafora type of progressive myoclonic epilepsy is an autosomal recessive disorder characterized by insidious onset of progressive neurodegeneration between 8 and 18 years of age. Initial features can include headache, difficulties in school work, myoclonic jerks, generalized seizures, and often visual hallucination. The myoclonus, seizures, and hallucinations gradually worsen and become intractable. This is accompanied by progressive cognitive decline, resulting in dementia. About 10 years after onset, affected individuals are in near-continuous myoclonus with absence seizures, frequent generalized seizures, and profound dementia or a vegetative state. Histologic studies of multiple tissues, including brain, muscle, liver, and heart show intracellular Lafora bodies, which are dense accumulations of malformed and insoluble glycogen molecules, termed polyglucosans (review by <a href="#9" class="mim-tip-reference" title="Ramachandran, N., Girard, J.-M., Turnbull, J., Minassian, B. A. <strong>The autosomal recessively inherited progressive myoclonus epilepsies and their genes.</strong> Epilepsia 50 (suppl.): 29-36, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19469843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19469843</a>] [<a href="https://doi.org/10.1111/j.1528-1167.2009.02117.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19469843">Ramachandran et al., 2009</a>). There is a slower progression of disease and later age at death in Lafora disease-2 than in Lafora disease-1 (MELF1, EPM2A; <a href="/entry/254780">254780</a>); see Genotype/Phenotype Correlations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19469843" 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>Myoclonic epilepsy of Lafora-1 is caused by mutation in the EPM2A gene (<a href="/entry/608072">608072</a>), which encodes laforin, on chromosome 6q24.</p><p>For a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (<a href="/entry/254800">254800</a>).</p>
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<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> reported detailed clinical characteristics of 17 patients with Lafora disease caused by mutations in the NHLRC1 gene. Age at onset ranged from 12 to 15 years, with the exception of 7 and 22 years in 2 patients. Seizures were the most common presentation, including generalized tonic-clonic seizures (50%); simple partial occipital seizures (18.7%); partial seizures with secondary generalization (12.4%); absence seizures (6.3%); and myoclonic seizures (6.3%). One patient presented with hepatic failure and did not develop neurologic symptoms. Other variable features included cognitive decline, inability to attend school, gait disturbance, inability to walk alone, and complete deterioration of mental status. <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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<p>In patients with Lafora disease, Lafora bodies are found in myoepithelial cells surrounding axillary apocrine (odoriferous) glands, whereas outside the axilla, Lafora bodies are found in the cells composing the ducts of the eccrine (perspiration) glands. In 2 unrelated patients with Lafora disease, one with mutation in the EPM2A gene and the other with mutation in the NHLRC1 gene, <a href="#1" class="mim-tip-reference" title="Andrade, D. M., Ackerley, C. A., Minett, T. S. C., Teive, H. A. G., Bohlega, S., Scherer, S. W., Minassian, B. A. <strong>Skin biopsy in Lafora disease: genotype-phenotype correlations and diagnostic pitfalls.</strong> Neurology 61: 1611-1614, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14663053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14663053</a>] [<a href="https://doi.org/10.1212/01.wnl.0000096017.19978.cb" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14663053">Andrade et al. (2003)</a> reported that the diagnosis had been made by Lafora bodies present in the myoepithelial cells of the axillary apocrine glands. In 2 other unrelated patients, each with mutations in the 2 different genes, the diagnosis of Lafora disease was made by Lafora bodies in the eccrine duct cells of forearm biopsies. The authors noted that patients with either genetic form of the disease have Lafora bodies in both apocrine myoepithelial cells and eccrine duct cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14663053" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Andrade, D. M., Ackerley, C. A., Minett, T. S. C., Teive, H. A. G., Bohlega, S., Scherer, S. W., Minassian, B. A. <strong>Skin biopsy in Lafora disease: genotype-phenotype correlations and diagnostic pitfalls.</strong> Neurology 61: 1611-1614, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14663053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14663053</a>] [<a href="https://doi.org/10.1212/01.wnl.0000096017.19978.cb" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14663053">Andrade et al. (2003)</a> reported a patient who had originally been diagnosed with an atypical form of Lafora disease (<a href="#4" class="mim-tip-reference" title="de Quadros, A., Sa, D. S., Kowacs, P. A., Teive, H. A. G., Werneck, L. C. <strong>Doenca de lafora E disturbios do movimento: relato de dois casos.</strong> Arq. Neuropsiquiatr. 58: 720-723, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973115</a>] [<a href="https://doi.org/10.1590/s0004-282x2000000400019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973115">de Quadros et al., 2000</a>) based on an axillary biopsy showing PAS-positive material in the cells lining the gland lumen, but not in myoepithelial cells or in eccrine glands. Mutation analysis showed that the patient actually had Unverricht-Lundborg disease (<a href="/entry/254800">254800</a>). <a href="#1" class="mim-tip-reference" title="Andrade, D. M., Ackerley, C. A., Minett, T. S. C., Teive, H. A. G., Bohlega, S., Scherer, S. W., Minassian, B. A. <strong>Skin biopsy in Lafora disease: genotype-phenotype correlations and diagnostic pitfalls.</strong> Neurology 61: 1611-1614, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14663053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14663053</a>] [<a href="https://doi.org/10.1212/01.wnl.0000096017.19978.cb" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14663053">Andrade et al. (2003)</a> noted the difficulty in diagnosing Lafora disease by axillary biopsy, and favored biopsy of skin outside the axilla. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14663053+10973115" 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="#2" class="mim-tip-reference" title="Chan, E. M., Bulman, D. E., Paterson, A. D., Turnbull, J., Andermann, E., Andermann, F., Rouleau, G. A., Delgado-Escueta, A. V., Scherer, S. W., Minassian, B. A. <strong>Genetic mapping of a new Lafora progressive myoclonus epilepsy locus (EPM2B) on 6p22.</strong> J. Med. Genet. 40: 671-675, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12960212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12960212</a>] [<a href="https://doi.org/10.1136/jmg.40.9.671" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12960212">Chan et al. (2003)</a> performed genomewide linkage analysis on 4 consanguineous French Canadian families with classic Lafora disease. A 2-point maximum lod score of 5.2 was obtained for a 2.2-Mb region on chromosome 6p22. All families shared the same 9 marker disease haplotype. The authors termed the locus EPM2B. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12960212" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transmission pattern of Lafora disease-2 in the families reported by <a href="#3" 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> was consistent with autosomal recessive inheritance. <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="#6" class="mim-tip-reference" title="Ganesh, S., Puri, R., Singh, S., Mittal, S., Dubey, D. <strong>Recent advances in the molecular basis of Lafora's progressive myoclonus epilepsy.</strong> J. Hum. Genet. 51: 1-8, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16311711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16311711</a>] [<a href="https://doi.org/10.1007/s10038-005-0321-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16311711">Ganesh et al. (2006)</a> and <a href="#10" class="mim-tip-reference" title="Singh, S., Ganesh, S. <strong>Lafora progressive myoclonus epilepsy: a meta-analysis of reported mutations in the first decade following discovery of the EPM2A and NHLRC1 genes.</strong> Hum. Mutat. 30: 715-723, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19267391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19267391</a>] [<a href="https://doi.org/10.1002/humu.20954" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19267391">Singh and Ganesh (2009)</a> provided detailed reviews of the molecular basis of Lafora disease, with specific review of the mutational spectrum of EPM2A and NHLRC1 genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16311711+19267391" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 34 probands with Lafora disease, <a href="#3" 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, including 8 deletions, 1 insertion, 7 missense changes, and 1 nonsense change (see, e.g., C26S, <a href="/entry/608072#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="/entry/608072#0005">608072.0005</a>-<a href="/entry/608072#0007">608072.0007</a>) in 23 of 25 patients with Lafora disease who did not have mutations in the laforin gene. P69A (<a href="/entry/608072#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="#12" 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="#12" 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="#11" 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>
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<p><a href="#3" 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 C26S mutation in the NHLRC1 gene in affected members of 4 French Canadian families with Lafora disease. Haplotype analysis indicated a founder effect. <a href="#11" 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 an additional French Canadian family with the C26S mutation, and they devised a DNA-based diagnostic test to screen for the C26S mutation for use in the French Canadian population. <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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<p>In a clinical analysis of patients with Lafora disease, <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> found that 21 patients with NHLRC1 mutations had a slightly longer disease course and later age at death compared to 70 patients from 54 families with EPM2A mutations. Two patients with NHLRC1 mutations reached the fourth decade of life. Among a total of 77 families with Lafora disease, 70.1% of probands had EPM2A mutations and 27.3% of probands had NHLRC1 mutations. No mutations in either gene were identified in 2 (2.6%) unrelated probands. <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="#11" 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> compared the clinical course of 13 patients with NHLRC1 mutations to 22 patients with EPM2A mutations. Although age at onset was similar in the 2 groups (approximately 12 years), patients with NHLRC1 mutations had a slower rate of disease progression and thus appeared to live longer. For example, respiratory assistance was required in patients with NHLRC1 and EPM2A mutations at a mean of 20 years and 6.5 years after disease onset, respectively. Cognitive decline, ataxia, and spasticity appeared 2 to 4 years after disease onset in both groups. <a href="#11" 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> postulated that malin, encoded by the NHLRC1 gene, may act upstream of laforin, encoded by the EPM2A gene, in a cellular cascade. <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>
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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="#8" 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. 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; <a href="/entry/608072">608072</a>). 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="#8" 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="#8" 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> described a canine epilepsy mutation that represents a tandem repeat expansion outside humans and devised a test to detect and counteract it 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="#13" class="mim-tip-reference" title="Valles-Ortega, J., Duran, J., Garcia-Rocha, M., Bosch, C., Saez, I., Pujadas, L., Serafin, A., Canas, X., Soriano, E., Delgado-Garcia, J. M., Gruart, A., Guinovart, J. J. <strong>Neurodegeneration and functional impairments associated with glycogen synthase accumulation in a mouse model of Lafora disease.</strong> EMBO Molec. Med. 3: 667-681, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21882344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21882344</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21882344[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/emmm.201100174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21882344">Valles-Ortega et al. (2011)</a> found that malin-knockout mice developed Lafora disease at around 11 months of age. Mutant animals showed neurodegeneration and seizures associated with Lafora bodies in several brain regions, including the hippocampus and cerebellum. Lafora bodies contained poorly branched glycogen and muscle glycogen synthase (GYS1; <a href="/entry/138570">138570</a>), particularly in the insoluble fraction. Lafora bodies were present in neurons, astrocytes, and interneurons. Malin-null mice showed increased susceptibility to kainate-induced epilepsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21882344" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Duran, J., Gruart, A., Garcia-Rocha, M., Delgado-Garcia, J. M., Guinovart, J. J. <strong>Glycogen accumulation underlies neurodegeneration and autophagy impairment in Lafora disease.</strong> Hum. Molec. Genet. 23: 3147-3156, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24452334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24452334</a>] [<a href="https://doi.org/10.1093/hmg/ddu024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24452334">Duran et al. (2014)</a> generated a double-transgenic mouse model in which malin was deleted in all tissues and Gys1 was specifically deleted in the brain. Glycogen content in the brain was significantly decreased in Gys1 heterozygous mice and was absent in Gys1 homozygous-null malin-knockout mice. Double-knockout mice did not show the increase in markers of neurodegeneration, the impairments in electrophysiologic properties of hippocampal synapses, or the susceptibility to kainate-induced epilepsy seen in the malin-knockout model, consistent with rescue from neurodegeneration. These mice also did not show impaired autophagy, as observed in malin-knockout mice. Additional mouse models with overaccumulation of glycogen showed impaired autophagy, suggesting that the accumulation of glycogen itself can cause autophagy impairment. The findings indicated that glycogen accumulation accounts for the neurodegeneration and functional consequences seen in the malin-knockout model, as well as the impaired autophagy. <a href="#5" class="mim-tip-reference" title="Duran, J., Gruart, A., Garcia-Rocha, M., Delgado-Garcia, J. M., Guinovart, J. J. <strong>Glycogen accumulation underlies neurodegeneration and autophagy impairment in Lafora disease.</strong> Hum. Molec. Genet. 23: 3147-3156, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24452334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24452334</a>] [<a href="https://doi.org/10.1093/hmg/ddu024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24452334">Duran et al. (2014)</a> suggested that regulation of glycogen synthesis may be a key target for the treatment of Lafora disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24452334" 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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Andrade, D. M., Ackerley, C. A., Minett, T. S. C., Teive, H. A. G., Bohlega, S., Scherer, S. W., Minassian, B. A.
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<strong>Skin biopsy in Lafora disease: genotype-phenotype correlations and diagnostic pitfalls.</strong>
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Neurology 61: 1611-1614, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14663053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14663053</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14663053" 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.0000096017.19978.cb" target="_blank">Full Text</a>]
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Chan, E. M., Bulman, D. E., Paterson, A. D., Turnbull, J., Andermann, E., Andermann, F., Rouleau, G. A., Delgado-Escueta, A. V., Scherer, S. W., Minassian, B. A.
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<strong>Genetic mapping of a new Lafora progressive myoclonus epilepsy locus (EPM2B) on 6p22.</strong>
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J. Med. Genet. 40: 671-675, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12960212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12960212</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12960212" 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.40.9.671" target="_blank">Full Text</a>]
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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.
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<strong>Mutations in NHLRC1 cause progressive myoclonus epilepsy.</strong>
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Nature Genet. 35: 125-127, 2003.
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[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>]
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[<a href="https://doi.org/10.1038/ng1238" target="_blank">Full Text</a>]
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de Quadros, A., Sa, D. S., Kowacs, P. A., Teive, H. A. G., Werneck, L. C.
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<strong>Doenca de lafora E disturbios do movimento: relato de dois casos.</strong>
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Arq. Neuropsiquiatr. 58: 720-723, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973115</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973115" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Duran, J., Gruart, A., Garcia-Rocha, M., Delgado-Garcia, J. M., Guinovart, J. J.
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<strong>Glycogen accumulation underlies neurodegeneration and autophagy impairment in Lafora disease.</strong>
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Hum. Molec. Genet. 23: 3147-3156, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24452334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24452334</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24452334" 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/ddu024" target="_blank">Full Text</a>]
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<strong>Recent advances in the molecular basis of Lafora's progressive myoclonus epilepsy.</strong>
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J. Hum. Genet. 51: 1-8, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16311711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16311711</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16311711" 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/s10038-005-0321-1" target="_blank">Full Text</a>]
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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.
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<strong>Lafora disease due to EPM2B mutations: a clinical and genetic study.</strong>
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Neurology 64: 982-986, 2005.
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[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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<a id="Lohi2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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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.
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<strong>Expanded repeat in canine epilepsy.</strong>
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Science 307: 81 only, 2005.
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[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="Ramachandran2009" class="mim-anchor"></a>
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<p class="mim-text-font">
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Ramachandran, N., Girard, J.-M., Turnbull, J., Minassian, B. A.
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<strong>The autosomal recessively inherited progressive myoclonus epilepsies and their genes.</strong>
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Epilepsia 50 (suppl.): 29-36, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19469843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19469843</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19469843" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1528-1167.2009.02117.x" target="_blank">Full Text</a>]
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<a id="Singh2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Singh, S., Ganesh, S.
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<strong>Lafora progressive myoclonus epilepsy: a meta-analysis of reported mutations in the first decade following discovery of the EPM2A and NHLRC1 genes.</strong>
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Hum. Mutat. 30: 715-723, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19267391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19267391</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19267391" 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.20954" target="_blank">Full Text</a>]
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<a id="Singh2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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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>
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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.
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<strong>Mutations in the NHLRC1 gene are the common cause for Lafora disease in the Japanese population.</strong>
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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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<a id="Valles-Ortega2011" class="mim-anchor"></a>
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<p class="mim-text-font">
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Valles-Ortega, J., Duran, J., Garcia-Rocha, M., Bosch, C., Saez, I., Pujadas, L., Serafin, A., Canas, X., Soriano, E., Delgado-Garcia, J. M., Gruart, A., Guinovart, J. J.
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<strong>Neurodegeneration and functional impairments associated with glycogen synthase accumulation in a mouse model of Lafora disease.</strong>
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EMBO Molec. Med. 3: 667-681, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21882344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21882344</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21882344[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=21882344" 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/emmm.201100174" target="_blank">Full Text</a>]
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Creation Date:
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Ada Hamosh : 01/17/2024
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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carol : 01/03/2025
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carol : 03/04/2024<br>carol : 03/01/2024<br>carol : 02/29/2024<br>carol : 01/25/2024<br>carol : 01/24/2024
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<strong>#</strong> 620681
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MYOCLONIC EPILEPSY OF LAFORA 2; MELF2
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EPILEPSY, PROGRESSIVE MYOCLONIC, 2B; EPM2B<br />
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LAFORA DISEASE 2
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<strong>Phenotype-Gene 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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6p22.3
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<span class="mim-font">
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Myoclonic epilepsy of Lafora 2
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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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NHLRC1
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<span class="mim-font">
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608072
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<strong>TEXT</strong>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because myoclonic epilepsy of Lafora-2 (MELF2), also known as progressive myoclonic epilepsy-2B (EPM2B), is caused by homozygous or compound heterozygous mutation in the NHLRC1 gene (608072), which encodes malin, on chromosome 6p22.</p>
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<strong>Description</strong>
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<span class="mim-text-font">
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<p>The Lafora type of progressive myoclonic epilepsy is an autosomal recessive disorder characterized by insidious onset of progressive neurodegeneration between 8 and 18 years of age. Initial features can include headache, difficulties in school work, myoclonic jerks, generalized seizures, and often visual hallucination. The myoclonus, seizures, and hallucinations gradually worsen and become intractable. This is accompanied by progressive cognitive decline, resulting in dementia. About 10 years after onset, affected individuals are in near-continuous myoclonus with absence seizures, frequent generalized seizures, and profound dementia or a vegetative state. Histologic studies of multiple tissues, including brain, muscle, liver, and heart show intracellular Lafora bodies, which are dense accumulations of malformed and insoluble glycogen molecules, termed polyglucosans (review by Ramachandran et al., 2009). There is a slower progression of disease and later age at death in Lafora disease-2 than in Lafora disease-1 (MELF1, EPM2A; 254780); see Genotype/Phenotype Correlations. </p><p>Myoclonic epilepsy of Lafora-1 is caused by mutation in the EPM2A gene (608072), which encodes laforin, on chromosome 6q24.</p><p>For a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800).</p>
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<h4>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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<p>Gomez-Abad et al. (2005) reported detailed clinical characteristics of 17 patients with Lafora disease caused by mutations in the NHLRC1 gene. Age at onset ranged from 12 to 15 years, with the exception of 7 and 22 years in 2 patients. Seizures were the most common presentation, including generalized tonic-clonic seizures (50%); simple partial occipital seizures (18.7%); partial seizures with secondary generalization (12.4%); absence seizures (6.3%); and myoclonic seizures (6.3%). One patient presented with hepatic failure and did not develop neurologic symptoms. Other variable features included cognitive decline, inability to attend school, gait disturbance, inability to walk alone, and complete deterioration of mental status. </p>
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<h4>
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<span class="mim-font">
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<strong>Diagnosis</strong>
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<span class="mim-text-font">
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<p>In patients with Lafora disease, Lafora bodies are found in myoepithelial cells surrounding axillary apocrine (odoriferous) glands, whereas outside the axilla, Lafora bodies are found in the cells composing the ducts of the eccrine (perspiration) glands. In 2 unrelated patients with Lafora disease, one with mutation in the EPM2A gene and the other with mutation in the NHLRC1 gene, Andrade et al. (2003) reported that the diagnosis had been made by Lafora bodies present in the myoepithelial cells of the axillary apocrine glands. In 2 other unrelated patients, each with mutations in the 2 different genes, the diagnosis of Lafora disease was made by Lafora bodies in the eccrine duct cells of forearm biopsies. The authors noted that patients with either genetic form of the disease have Lafora bodies in both apocrine myoepithelial cells and eccrine duct cells. </p><p>Andrade et al. (2003) reported a patient who had originally been diagnosed with an atypical form of Lafora disease (de Quadros et al., 2000) based on an axillary biopsy showing PAS-positive material in the cells lining the gland lumen, but not in myoepithelial cells or in eccrine glands. Mutation analysis showed that the patient actually had Unverricht-Lundborg disease (254800). Andrade et al. (2003) noted the difficulty in diagnosing Lafora disease by axillary biopsy, and favored biopsy of skin outside the axilla. </p>
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<div>
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<br />
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</h4>
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<span class="mim-text-font">
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<p>Chan et al. (2003) performed genomewide linkage analysis on 4 consanguineous French Canadian families with classic Lafora disease. A 2-point maximum lod score of 5.2 was obtained for a 2.2-Mb region on chromosome 6p22. All families shared the same 9 marker disease haplotype. The authors termed the locus EPM2B. </p>
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<h4>
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<strong>Inheritance</strong>
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<p>The transmission pattern of Lafora disease-2 in the families reported by Chan et al. (2003) was consistent with autosomal recessive inheritance. </p>
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<strong>Molecular Genetics</strong>
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<p>Ganesh et al. (2006) and Singh and Ganesh (2009) provided detailed reviews of the molecular basis of Lafora disease, with specific review of the mutational spectrum of EPM2A and NHLRC1 genes. </p><p>In 34 probands with Lafora disease, Chan et al. (2003) identified 17 different mutations in the NHLRC1 gene in 26 families, including 8 deletions, 1 insertion, 7 missense changes, and 1 nonsense change (see, e.g., C26S, 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>
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<strong>Population Genetics</strong>
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<p>Chan et al. (2003) identified a homozygous C26S mutation in the NHLRC1 gene in affected members of 4 French Canadian families with Lafora disease. Haplotype analysis indicated a founder effect. Singh et al. (2006) identified an additional French Canadian family with the C26S mutation, and they devised a DNA-based diagnostic test to screen for the C26S mutation for use in the French Canadian population. </p>
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<strong>Genotype/Phenotype Correlations</strong>
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<p>In a clinical analysis of patients with Lafora disease, Gomez-Abad et al. (2005) found that 21 patients with NHLRC1 mutations had a slightly longer disease course and later age at death compared to 70 patients from 54 families with EPM2A mutations. Two patients with NHLRC1 mutations reached the fourth decade of life. Among a total of 77 families with Lafora disease, 70.1% of probands had EPM2A mutations and 27.3% of probands had NHLRC1 mutations. No mutations in either gene were identified in 2 (2.6%) unrelated probands. </p><p>Singh et al. (2006) compared the clinical course of 13 patients with NHLRC1 mutations to 22 patients with EPM2A mutations. Although age at onset was similar in the 2 groups (approximately 12 years), patients with NHLRC1 mutations had a slower rate of disease progression and thus appeared to live longer. For example, respiratory assistance was required in patients with NHLRC1 and EPM2A mutations at a mean of 20 years and 6.5 years after disease onset, respectively. Cognitive decline, ataxia, and spasticity appeared 2 to 4 years after disease onset in both groups. Singh et al. (2006) postulated that malin, encoded by the NHLRC1 gene, may act upstream of laforin, encoded by the EPM2A gene, in a cellular cascade. </p>
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<strong>Animal Model</strong>
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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. 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; 608072). 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) described a canine epilepsy mutation that represents a tandem repeat expansion outside humans and devised a test to detect and counteract it through controlled breeding. </p><p>Valles-Ortega et al. (2011) found that malin-knockout mice developed Lafora disease at around 11 months of age. Mutant animals showed neurodegeneration and seizures associated with Lafora bodies in several brain regions, including the hippocampus and cerebellum. Lafora bodies contained poorly branched glycogen and muscle glycogen synthase (GYS1; 138570), particularly in the insoluble fraction. Lafora bodies were present in neurons, astrocytes, and interneurons. Malin-null mice showed increased susceptibility to kainate-induced epilepsy. </p><p>Duran et al. (2014) generated a double-transgenic mouse model in which malin was deleted in all tissues and Gys1 was specifically deleted in the brain. Glycogen content in the brain was significantly decreased in Gys1 heterozygous mice and was absent in Gys1 homozygous-null malin-knockout mice. Double-knockout mice did not show the increase in markers of neurodegeneration, the impairments in electrophysiologic properties of hippocampal synapses, or the susceptibility to kainate-induced epilepsy seen in the malin-knockout model, consistent with rescue from neurodegeneration. These mice also did not show impaired autophagy, as observed in malin-knockout mice. Additional mouse models with overaccumulation of glycogen showed impaired autophagy, suggesting that the accumulation of glycogen itself can cause autophagy impairment. The findings indicated that glycogen accumulation accounts for the neurodegeneration and functional consequences seen in the malin-knockout model, as well as the impaired autophagy. Duran et al. (2014) suggested that regulation of glycogen synthesis may be a key target for the treatment of Lafora disease. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<ol>
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|
|
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|
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<p class="mim-text-font">
|
|
Andrade, D. M., Ackerley, C. A., Minett, T. S. C., Teive, H. A. G., Bohlega, S., Scherer, S. W., Minassian, B. A.
|
|
<strong>Skin biopsy in Lafora disease: genotype-phenotype correlations and diagnostic pitfalls.</strong>
|
|
Neurology 61: 1611-1614, 2003.
|
|
|
|
|
|
[PubMed: 14663053]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000096017.19978.cb]
|
|
|
|
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|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
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|
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Chan, E. M., Bulman, D. E., Paterson, A. D., Turnbull, J., Andermann, E., Andermann, F., Rouleau, G. A., Delgado-Escueta, A. V., Scherer, S. W., Minassian, B. A.
|
|
<strong>Genetic mapping of a new Lafora progressive myoclonus epilepsy locus (EPM2B) on 6p22.</strong>
|
|
J. Med. Genet. 40: 671-675, 2003.
|
|
|
|
|
|
[PubMed: 12960212]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.40.9.671]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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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: 12958597]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1238]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Quadros, A., Sa, D. S., Kowacs, P. A., Teive, H. A. G., Werneck, L. C.
|
|
<strong>Doenca de lafora E disturbios do movimento: relato de dois casos.</strong>
|
|
Arq. Neuropsiquiatr. 58: 720-723, 2000.
|
|
|
|
|
|
[PubMed: 10973115]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1590/s0004-282x2000000400019]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Duran, J., Gruart, A., Garcia-Rocha, M., Delgado-Garcia, J. M., Guinovart, J. J.
|
|
<strong>Glycogen accumulation underlies neurodegeneration and autophagy impairment in Lafora disease.</strong>
|
|
Hum. Molec. Genet. 23: 3147-3156, 2014.
|
|
|
|
|
|
[PubMed: 24452334]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddu024]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ganesh, S., Puri, R., Singh, S., Mittal, S., Dubey, D.
|
|
<strong>Recent advances in the molecular basis of Lafora's progressive myoclonus epilepsy.</strong>
|
|
J. Hum. Genet. 51: 1-8, 2006.
|
|
|
|
|
|
[PubMed: 16311711]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10038-005-0321-1]
|
|
|
|
|
|
</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]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.WNL.0000154519.10805.F7]
|
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</p>
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</li>
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<li>
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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.
|
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|
|
|
|
[PubMed: 15637270]
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[Full Text: https://doi.org/10.1126/science.1102832]
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</p>
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</li>
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|
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<li>
|
|
<p class="mim-text-font">
|
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Ramachandran, N., Girard, J.-M., Turnbull, J., Minassian, B. A.
|
|
<strong>The autosomal recessively inherited progressive myoclonus epilepsies and their genes.</strong>
|
|
Epilepsia 50 (suppl.): 29-36, 2009.
|
|
|
|
|
|
[PubMed: 19469843]
|
|
|
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|
|
[Full Text: https://doi.org/10.1111/j.1528-1167.2009.02117.x]
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</p>
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</li>
|
|
|
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<li>
|
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<p class="mim-text-font">
|
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Singh, S., Ganesh, S.
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<strong>Lafora progressive myoclonus epilepsy: a meta-analysis of reported mutations in the first decade following discovery of the EPM2A and NHLRC1 genes.</strong>
|
|
Hum. Mutat. 30: 715-723, 2009.
|
|
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|
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[PubMed: 19267391]
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[Full Text: https://doi.org/10.1002/humu.20954]
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</p>
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<li>
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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.
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[PubMed: 16950819]
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[Full Text: https://doi.org/10.1136/jmg.2005.039479]
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</p>
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</li>
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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.
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<strong>Mutations in the NHLRC1 gene are the common cause for Lafora disease in the Japanese population.</strong>
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J. Hum. Genet. 50: 347-352, 2005.
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[PubMed: 16021330]
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[Full Text: https://doi.org/10.1007/s10038-005-0263-7]
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Valles-Ortega, J., Duran, J., Garcia-Rocha, M., Bosch, C., Saez, I., Pujadas, L., Serafin, A., Canas, X., Soriano, E., Delgado-Garcia, J. M., Gruart, A., Guinovart, J. J.
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<strong>Neurodegeneration and functional impairments associated with glycogen synthase accumulation in a mouse model of Lafora disease.</strong>
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EMBO Molec. Med. 3: 667-681, 2011.
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[PubMed: 21882344]
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[Full Text: https://doi.org/10.1002/emmm.201100174]
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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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