title: SCN8A mutations in Chinese children with early onset epilepsy and intellectual disability.
abstract: OBJECTIVE
  Mutations in SCN8A, 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 SCN8A mutations in Chinese patients with epilepsy of unknown etiology and ID/DD.
  
  
  METHODS
  We used targeted next-generation sequencing to identify SCN8A 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 SCN8A mutations in our cohort and analyzed their clinical data.
  
  
  RESULTS
  Five de novo SCN8A 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.
  
  
  CONCLUSIONS
  Five SCN8A mutations were first reported in Chinese patients with epilepsy and ID/DD, expanding the phenotype and mutation spectrum of SCN8A 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 SCN8A 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 SCN8A mutations.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Weijing
authors.initials: W
authors.lastname: Kong
authors.forename: Yujia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.forename: Kai
authors.initials: K
authors.lastname: Gao
authors.forename: Han
authors.initials: H
authors.lastname: Xie
authors.forename: Jingmin
authors.initials: J
authors.lastname: Wang
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiru
authors.initials: X
authors.lastname: Wu
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use; D044466:Asian People; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D004827:Epilepsy / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D062557:NAV1.6 Voltage-Gated Sodium Channel / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D000927:Anticonvulsants; D062557:NAV1.6 Voltage-Gated Sodium Channel; C100681:SCN8A protein, human
keywords: Epilepsy; Intellectual disability; SCN8A; Sodium channel blocker