{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:13:15Z","timestamp":1791349995884,"version":"4.3.1"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,6,2]],"date-time":"2014-06-02T00:00:00Z","timestamp":1401667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of Health, Labour and Welfare of Japan"},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["25293085"],"award-info":[{"award-number":["25293085"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["25293235"],"award-info":[{"award-number":["25293235"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["13313587"],"award-info":[{"award-number":["13313587"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["24591500"],"award-info":[{"award-number":["24591500"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Strategic Research Program for Brain Sciences","award":["11105137"],"award-info":[{"award-number":["11105137"]}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology of Japan","doi-asserted-by":"crossref","award":["12024421"],"award-info":[{"award-number":["12024421"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,7]]},"abstract":"Summary<\/jats:title>Objective<\/jats:title>De novo SCN8A<\/jats:italic><\/jats:styled-content> mutations have been reported in patients with epileptic encephalopathy. Herein we report seven patients with de novo heterozygous SCN8A<\/jats:italic><\/jats:styled-content> mutations, which were found in our comprehensive genetic analysis (target capture or whole\u2010exome sequencing) for early onset epileptic encephalopathies (EOEE<\/jats:styled-content>s).<\/jats:p><\/jats:sec>Methods<\/jats:title>A total of 163 patients with EOEE<\/jats:styled-content>s without mutations in known genes, including 6 with malignant migrating partial seizures in infancy (MMPSI<\/jats:styled-content>), and 60 with unclassified EOEE<\/jats:styled-content>s, were analyzed by target capture (28 samples) or whole\u2010exome sequencing (135 samples).<\/jats:p><\/jats:sec>Results<\/jats:title>We identified de novo SCN8A<\/jats:italic><\/jats:styled-content> mutations in 7 patients: 6 of 60 unclassified EOEE<\/jats:styled-content>s (10.0%), and one of 6 MMPSI<\/jats:styled-content> cases (16.7%). The mutations were scattered through the entire gene: four mutations were located in linker regions, two in the fourth transmembrane segments, and one in the C<\/jats:styled-content>\u2010terminal domain. The type of the initial seizures was variable including generalized tonic\u2013clonic, atypical absence, partial, apneic attack, febrile convulsion, and loss of tone and consciousness. Onset of seizures was during the neonatal period in two patients, and between 3 and 7\u00a0months of age in five patients. Brain magnetic resonance imaging (MRI)<\/jats:styled-content> showed cerebellar and cerebral atrophy in one and six patients, respectively. All patients with SCN8A<\/jats:italic><\/jats:styled-content> missense mutations showed initially uncontrollable seizures by any drugs, but eventually one was seizure\u2010free and three were controlled at the last examination. All patients showed developmental delay or regression in infancy, resulting in severe intellectual disability.<\/jats:p><\/jats:sec>Significance<\/jats:title>Our data reveal that SCN8A<\/jats:italic><\/jats:styled-content> mutations can cause variable phenotypes, most of which can be diagnosed as unclassified EOEE<\/jats:styled-content>s, and rarely as MMPSI<\/jats:styled-content>. Together with previous reports, our study further indicates that genetic testing of SCN8A<\/jats:italic><\/jats:styled-content> should be considered in children with unclassified severe epilepsy.<\/jats:p>A PowerPoint slide summarizing this article is available for download in the Supporting Information section here<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12668","type":"journal-article","created":{"date-parts":[[2014,6,2]],"date-time":"2014-06-02T22:05:59Z","timestamp":1401746759000},"page":"994-1000","source":"Crossref","is-referenced-by-count":130,"title":["Early onset epileptic encephalopathy caused by de novo SCN<\/scp>8A<\/i> mutations"],"prefix":"10.1111","volume":"55","author":[{"given":"Chihiro","family":"Ohba","sequence":"first","affiliation":[{"name":"Department of Human Genetics Graduate School of Medicine Yokohama City University Yokohama Japan"},{"name":"Department of Clinical Neurology and Stroke Medicine Yokohama City University Yokohama 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