De novoGABRA1mutations in Ohtahara and West syndromes
| Autor: | Hirofumi Kodera, Noriko Miyake, Akihiko Ishiyama, Kosuke Kohashi, Atsuo Kikuchi, Taro Kitamura, Mitsuhiro Kato, Hirotaka Motoi, Saoko Takeshita, Kazuhiro Haginoya, Yoshinori Tsurusaki, Toshiyuki Maeda, Naomi Hino-Fukuyo, Naomichi Matsumoto, Muneaki Matsuo, Mitsuko Nakashima, Chihiro Ohba, Daisuke Tajima, Hirotomo Saitsu, Kaoru Araki, Masayuki Sasaki, Shigeo Kure |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Ohtahara syndrome Pediatrics medicine.medical_specialty Molecular Sequence Data Mutation Missense medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Childhood absence epilepsy Dravet syndrome medicine Humans Missense mutation Amino Acid Sequence Generalized epilepsy Child Genetics Mutation business.industry Infant Electroencephalography West Syndrome Receptors GABA-A medicine.disease 030104 developmental biology Neurology Child Preschool Female Neurology (clinical) Juvenile myoclonic epilepsy business Spasms Infantile 030217 neurology & neurosurgery |
| Zdroj: | Epilepsia. 57:566-573 |
| ISSN: | 0013-9580 |
| Popis: | SummaryObjective 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. |
| Databáze: | OpenAIRE |
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