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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2013-08-26T00:00:00-04:00" class="date-display-single">August 26, 2013</span></p><div class='syndicate'><h1>Insights Into Genetic Causes of Childhood Epilepsies</h1><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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</div><p>A new study linked 2 novel genes to severe forms of childhood epilepsies. The results provide opportunities for exploring the origins and treatment of the disorders.</p>
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<p>Epilepsy is a group of neurological disorders caused by misfiring nerve cells in the brain. When the normal pattern of nerve activity becomes disturbed, it can produce debilitating convulsions and a range of other symptoms. More than 2 million people in the United States suffer from epilepsy, with children being most affected.</p>
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<p>Identifying genes that may affect childhood epilepsy has been difficult. Many disease-linked genes have been found by tracking down mutations that are inherited along with the disease. However, the genetic mutations associated with childhood epilepsies tend to be new mutations that aren’t inherited — called spontaneous, or de novo, mutations.</p>
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<p>The new study is a combined effort of 2 major projects to find the genetic causes of epilepsy, called Epilepsy 4000 and the Epilepsy Phenome/Genome Project. Largely funded by NIH’s National Institute of Neurological Disorders and Stroke (NINDS), researchers have collected DNA and clinical data from thousands of epilepsy patients and their relatives.</p>
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<p>In this study, the researchers searched for mutations that are likely to cause 2 classical forms of epilepsy: infantile spasms and Lennox-Gastaut syndrome. The scientists compared the exomes (the protein-coding sections of the genome) of 264 epileptic children with those of their healthy parents to identify non-inherited, de novo mutations. The results appeared online in <em>Nature</em> on August 11, 2013.</p>
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<p>The researchers observed mutations in several candidate genes. Advanced analysis techniques helped them identify 6 genes associated with the epilepsies. Four of these genes had already been linked to epilepsy, but 2 hadn’t (<em>ALG13</em> and <em>GABRB3</em>). When the researchers looked at these 6 genes in healthy families, they found no significant excess of de novo mutations.</p>
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<p>A deeper and broader analysis of the mutations helped the researchers estimate that up to 90 genes could carry epilepsy-causing mutations. They were also able to identify specific molecular pathways that may be involved in the disorder. This knowledge could lead to candidate drug targets for new treatments.</p>
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<p>“We anticipate that further studies will identify many new disease-causing genes, and we intend to develop a watch list of the genes which summarizes their clinical characteristics in a way that will be helpful for doctors, patients and researchers,” says Dr. David Goldstein of Duke University Medical Center, a leader of the study.</p>
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</div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="http://www.ninds.nih.gov/disorders/epilepsy/epilepsy.htm" target="_top">Epilepsy</a></li><li><a href="http://www.ninds.nih.gov/health_and_medical/disorders/infantilespasms.htm" target="_top">Infantile Spasms Information Page</a></li><li><a href="http://www.ninds.nih.gov/health_and_medical/disorders/lennoxgastautsyndrome_doc.htm" target="_top">Lennox-Gastaut Syndrome</a></li><li><a href="http://www.epgp.org/" target="_top">Epilepsy Phenome/Genome Project</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="http://www.ncbi.nlm.nih.gov/pubmed/23934111"> Nature.</a> 2013 Aug 11. doi: 10.1038/nature12439. [Epub ahead of print] PMID: 23934111.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute of Neurological Disorders and Stroke (NINDS); Finding a Cure for Epilepsy and Seizures; and the Richard Thalheimer Philanthropic Fund.</p>
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<h3 class="block__title">About NIH Research Matters</h3>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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<p>ISSN 2375-9593</p>
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