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SCN 8A mutations in Chinese children with early onset epilepsy and intellectual disability
Author(s) -
Kong Weijing,
Zhang Yujia,
Gao Yang,
Liu Xiaoyan,
Gao Kai,
Xie Han,
Wang Jingmin,
Wu Ye,
Zhang Yuehua,
Wu Xiru,
Jiang Yuwu
Publication year - 2015
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.12925
Subject(s) - epilepsy , sanger sequencing , intellectual disability , etiology , mutation , medicine , genetics , cohort , bioinformatics , pediatrics , gene , biology , psychiatry
Summary Objective Mutations in SCN 8A , a voltage‐gated sodium‐channel type VIII alpha subunit gene, have recently been recognized as one of the pathogenic mechanisms leading to epilepsy and intellectual/developmental disabilities ( IDDs ). The aim of this study was to detect SCN 8A mutations in Chinese patients with epilepsy of unknown etiology and ID / DD . Methods We used targeted next‐generation sequencing to identify SCN 8A mutations in Chinese patients with epilepsy of unknown etiology and IDDs . A filter process was performed to prioritize rare variants of potential functional significance. Sanger sequencing confirmed the variants and determined the parental origin. We followed all patients with SCN 8A mutations in our cohort and analyzed their clinical data. Results Five de novo SCN 8A mutations were identified, including four novel mutations (p.Ala890Thr, p.Leu407Phe, p.Arg850Gln, and p.Ser1596Cys) and one reported (p.Arg1617Gln). Polyphen2 and SIFT software predicted that all five mutations probably damaged Nav1.6 protein function; Mutation Taster indicated that all mutations were disease‐causing. Three of these five patients were controlled well by sodium channel blockers ( SCBs ). Two of these three patients remained seizure free for 6 and 1.5 months, respectively. One patient had sudden unexpected death in epilepsy ( SUDEP ) at the age of 1 year and 4 months. Significance Five SCN 8A mutations were first reported in Chinese patients with epilepsy and ID / DD , expanding the phenotype and mutation spectrum of SCN 8A mutations. Although three of these patients were controlled well by SCBs in our study, the effectiveness of SCBs should be validated in more patients with epilepsy caused by SCN 8A mutations in the future. One of our five patients had sudden unexpected death in epilepsy SUDEP , suggesting that we should pay more attention to SUDEP in epileptic patients with SCN 8A mutations.