Premium
De novo GABRA1 mutations in Ohtahara and West syndromes
Author(s) -
Kodera Hirofumi,
Ohba Chihiro,
Kato Mitsuhiro,
Maeda Toshiyuki,
Araki Kaoru,
Tajima Daisuke,
Matsuo Muneaki,
HinoFukuyo Naomi,
Kohashi Kosuke,
Ishiyama Akihiko,
Takeshita Saoko,
Motoi Hirotaka,
Kitamura Taro,
Kikuchi Atsuo,
Tsurusaki Yoshinori,
Nakashima Mitsuko,
Miyake Noriko,
Sasaki Masayuki,
Kure Shigeo,
Haginoya Kazuhiro,
Saitsu Hirotomo,
Matsumoto Naomichi
Publication year - 2016
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.13344
Subject(s) - west syndrome , dravet syndrome , epilepsy , missense mutation , medicine , pediatrics , myoclonic epilepsy , juvenile myoclonic epilepsy , mutation , childhood absence epilepsy , encephalopathy , genetics , biology , psychiatry , gene
Summary Objective GABRA 1 mutations have been identified in patients with familial juvenile myoclonic epilepsy, sporadic childhood absence epilepsy, and idiopathic familial generalized epilepsy. In addition, de novo GABRA 1 mutations were recently reported in a patient with infantile spasms and four patients with Dravet syndrome. Those reports suggest that GABRA 1 mutations are associated with infantile epilepsy including early onset epileptic encephalopathies. In this study, we searched for GABRA 1 mutations in patients with infantile epilepsy to investigate the phenotypic spectrum of GABRA 1 mutations. Methods In total, 526 and 145 patients with infantile epilepsy were analyzed by whole‐exome sequencing and GABRA 1 ‐targeted resequencing, respectively. Results We identified five de novo missense GABRA 1 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 ( TM 1) were identified in three unrelated patients with West syndrome and a patient with Ohtahara syndrome, respectively; and p.V287L in TM 2 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 GABRA 1 mutations can cause early onset epileptic encephalopathies, including Ohtahara syndrome and West syndrome.