{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:38:48Z","timestamp":1791250728834,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Renate Maass foundation","award":["Not available"],"award-info":[{"award-number":["Not available"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Epilepsy is a phenotypically and genetically highly heterogeneous disorder with &gt;200 genes linked to inherited forms of the disease. To identify the underlying genetic cause in a patient with intractable seizures, optic atrophy, severe intellectual disability (<jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content>), brain abnormalities, and muscular hypotonia, we performed exome sequencing in a 5\u2010year\u2010old girl and her unaffected parents. In the patient, we detected a novel, de novo missense mutation in the <jats:italic><jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content><\/jats:italic> (c.5645<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>&gt;<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>; p.<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>1882<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>) gene encoding the \u03b1<jats:styled-content style=\"fixed-case\"><jats:sub>II<\/jats:sub><\/jats:styled-content>\u2010subunit of the voltage\u2010gated sodium channel <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>a<jats:sub>v<\/jats:sub>1.2. A literature review revealed 33 different <jats:italic><jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content><\/jats:italic> mutations in 14 families with benign forms of epilepsy and in 21 cases with severe phenotypes. Although almost all benign mutations were inherited, the majority of severe mutations occurred de novo. Of interest, de novo <jats:italic><jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content><\/jats:italic> mutations have also been reported in five patients without seizures but with <jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content> (n\u00a0=\u00a03) and\/or autism (n\u00a0=\u00a03). In the present study, we successfully used exome sequencing to detect a de novo mutation in a genetically heterogeneous disorder with epilepsy and <jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content>. Using this approach, we expand the phenotypic spectrum of <jats:italic><jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content><\/jats:italic> mutations. Our own and literature data indicate that <jats:italic><jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content><\/jats:italic>\u2010linked severe phenotypes are more likely to be caused by de novo mutations.<\/jats:p><jats:p>A PowerPoint slide summarizing this article is available for download in the Supporting Information section <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1111\/epi.12554\/suppinfo\">here<\/jats:ext-link>.<\/jats:p>","DOI":"10.1111\/epi.12554","type":"journal-article","created":{"date-parts":[[2014,3,3]],"date-time":"2014-03-03T09:34:59Z","timestamp":1393839299000},"source":"Crossref","is-referenced-by-count":66,"title":["Exome sequencing identifies a de novo <i><scp>SCN<\/scp>2<scp>A<\/scp><\/i> mutation in a patient with intractable seizures, severe intellectual disability, optic atrophy, muscular hypotonia, and brain abnormalities"],"prefix":"10.1111","volume":"55","author":[{"given":"Anna\u2010Lena","family":"Baasch","sequence":"first","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"H\u00fcning","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik Universit\u00e4t zu L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Gilissen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Nijmegen Center for Molecular Life Sciences Institute for Genetic and Metabolic Disease Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Klepper","sequence":"additional","affiliation":[{"name":"Children's Hospital Aschaffenburg Aschaffenburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris A.","family":"Veltman","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Nijmegen Center for Molecular Life Sciences Institute for Genetic and Metabolic Disease Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Gillessen\u2010Kaesbach","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik Universit\u00e4t zu L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Hoischen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Nijmegen Center for Molecular Life Sciences Institute for Genetic and Metabolic Disease Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Lohmann","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03631.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0351077"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09534"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-101519"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3241"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61480-9"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12201"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.712"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dys202"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10945"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2646"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3089-03.2004"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.111065098"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03516.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20029"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq057"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181f8812e"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12137"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2009.08.009"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01049.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181b9cebc"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2012.06.006"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2006.00392.x"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2012.04.016"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)09968-3"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1206524"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-100819"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12089"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(01)00312-6"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.12554","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.12554","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T22:49:05Z","timestamp":1696286945000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.12554"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,4]]}},"alternative-id":["10.1111\/epi.12554"],"URL":"https:\/\/doi.org\/10.1111\/epi.12554","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3]]}}}