@article{3b02daae2c2b46daafbd4dce0f570b2a,
title = "De novo GABRA1 mutations in Ohtahara and West syndromes",
abstract = "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.",
keywords = "De novo mutation, Early onset epileptic encephalopathy, GABA receptor, GABRA1, Infantile epilepsy",
author = "Hirofumi Kodera and Chihiro Ohba and Mitsuhiro Kato and Toshiyuki Maeda and Kaoru Araki and Daisuke Tajima and Muneaki Matsuo and Naomi Hino-Fukuyo and Kosuke Kohashi and Akihiko Ishiyama and Saoko Takeshita and Hirotaka Motoi and Taro Kitamura and Atsuo Kikuchi and Yoshinori Tsurusaki and Mitsuko Nakashima and Noriko Miyake and Masayuki Sasaki and Shigeo Kure and Kazuhiro Haginoya and Hirotomo Saitsu and Naomichi Matsumoto",
note = "Funding Information: Acknowledgments: We would like to thank the patients and their families for their participation in this study. We also thank Dr. P. Cossette (Universit? de Montr?al) and Dr. D. Bowie (McGill University) for kindly providing the cDNAs of GABRB2 and GABRG2 used in this study, and Nobuko Watanabe and Mai Sato for their excellent technical assistance. This work is supported in part by a grant for Research on Measures for Intractable Diseases (14525125), a grant for Comprehensive Research on Disability Health and Welfare (13802019), the Strategic Research Program for Brain Science (SRPBS) (11105137) and Practical Research Project for Rare/Intractable Diseases (27280301) from the Japan Agency for Medical Research and Development (AMED); a Grant-in-Aid for Scientific Research on Innovative Areas (Transcription Cycle) (24118007) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); Grants-in-Aid for Scientific Research (B) (25293085, 25293235) and (A) (13313587), challenging Exploratory Research (26670505) and Young Scientists (B) (26860816) from the Japan Society for the Promotion of Science (JSPS); the fund for Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems (11105305) from the Japan Science and Technology Agency (JST); and the Takeda Science Foundation. Publisher Copyright: {\textcopyright} Wiley Periodicals, Inc.",
year = "2016",
month = apr,
day = "1",
doi = "10.1111/epi.13344",
language = "English",
volume = "57",
pages = "566--573",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley-Blackwell",
number = "4",
}