Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome

• DOI: 10.1212/wnl.0b013e3182a43e57
• Publication Date: 2013-08-10T04:43:15Z
• Authors: Kazuyuki Nakamura; Mitsuhiro Kato; Hitoshi Osaka; Sumimasa Yamashita; Eiji Nakagawa; Kazuhiro Haginoya; Jun Tohyama; Mitsuko Okuda; Takahito Wada; Shuichi Shimakawa; Katsumi Imai; Saoko Takeshita; Hisako Ishiwata; Dorit Lev; Tally Lerman-Sagie; David E. Cervante...; Camilo E. Villarroel; Masaharu Ohfu; Karin Writzl; Barbara Gnidovec ...; Shinichi Hirabayashi; David Chitayat; Diane Myles Reid; Kiyomi Nishiyama; Hirofumi Kodera; Mitsuko Nakashima; Yoshinori Tsurusaki; Noriko Miyake; Kiyoshi Hayasaka; Naomichi Matsumoto; Hirotomo Saitsu
• Keywords: Male; NAV1.2 Voltage-Gated Sodium Channel; Infant, Newborn; Brain; Infant; Electroencephalography; Magnetic Resonance Imaging; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Mutation; Humans; Female; Spasms, Infantile

<h3>Objective:</h3> We aimed to investigate the possible association between <i>SCN2A</i> mutations and early-onset epileptic encephalopathies (EOEEs). <h3>Methods:</h3> recruited a total of 328 patients with EOEE, including 67 Ohtahara syndrome (OS) 150 West syndrome. were examined using high resolution melt analysis or whole exome sequencing. <h3>Results:</h3> found 14 novel missense in 15 patients: 9 OS cases (13.4%), 1 (0.67%), 5 111 unclassified EOEEs (4.5%). Twelve confirmed as de novo, all absent 212 control exomes. A novo mosaic mutation (c.3976G&gt;C) mutant allele frequency 18% was detected one patient. One (c.634A&gt;G) transcript variant 3, which is neonatal isoform. All located linker regions 2 transmembrane segments. In 7 OS, EEG findings transitioned from suppression-burst pattern hypsarrhythmia. had intractable seizures; 3 them seizure-free at last medical examination. showed severe developmental delay. <h3>Conclusions:</h3> Our study that are an important genetic cause OS. Given wide clinical spectrum associated mutations, testing for should be considered children different conditions.