De novo GABRA1 mutations in Ohtahara and West syndromes

Hirofumi Kodera, Chihiro Ohba, Mitsuhiro Kato, Toshiyuki Maeda, Kaoru Araki, Daisuke Tajima, Muneaki Matsuo, Naomi Hino-Fukuyo, Kosuke Kohashi, Akihiko Ishiyama, Saoko Takeshita, Hirotaka Motoi, Taro Kitamura, Atsuo Kikuchi, Yoshinori Tsurusaki, Mitsuko Nakashima, Noriko Miyake, Masayuki Sasaki, Shigeo Kure, Kazuhiro HaginoyaHirotomo Saitsu, Naomichi Matsumoto

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)


Objective GABRA1 mutations have been identified in patients with familial juvenile myoclonic epilepsy, sporadic childhood absence epilepsy, and idiopathic familial generalized epilepsy. In addition, de novo GABRA1 mutations were recently reported in a patient with infantile spasms and four patients with Dravet syndrome. Those reports suggest that GABRA1 mutations are associated with infantile epilepsy including early onset epileptic encephalopathies. In this study, we searched for GABRA1 mutations in patients with infantile epilepsy to investigate the phenotypic spectrum of GABRA1 mutations. Methods In total, 526 and 145 patients with infantile epilepsy were analyzed by whole-exome sequencing and GABRA1-targeted resequencing, respectively. Results We identified five de novo missense GABRA1 mutations in six unrelated patients. A p.R112Q mutation in the long extracellular N-terminus was identified in a patient with infantile epilepsy; p.P260L, p.M263T, and p.M263I in transmembrane spanning domain 1 (TM1) were identified in three unrelated patients with West syndrome and a patient with Ohtahara syndrome, respectively; and p.V287L in TM2 was identified in a patient with unclassified early onset epileptic encephalopathy. Four of these mutations have not been observed previously. Significance Our study suggests that de novo GABRA1 mutations can cause early onset epileptic encephalopathies, including Ohtahara syndrome and West syndrome.

Original languageEnglish
Pages (from-to)566-573
Number of pages8
Issue number4
Publication statusPublished - 2016 Apr 1


  • De novo mutation
  • Early onset epileptic encephalopathy
  • GABA receptor
  • GABRA1
  • Infantile epilepsy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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