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ID 56950
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著者
Ohmori, Iori Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 科研費研究者番号
Ouchida, Mamoru Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 科研費研究者番号
Kobayashi, Katsuhiro
Jitsumori, Yoshimi
Mori, Akiko Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Michiue, Hiroyuki Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 科研費研究者番号
Nishiki, Teiichi Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 科研費研究者番号
Ohtsuka, Yoko
Matsui, Hideki Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 科研費研究者番号
抄録
Dravet syndrome is an intractable epileptic syndrome beginning in the first year of life. De novo mutations of SCN1A, which encode the Na(v)1.1 neuronal voltage-gated sodium channel, are considered the major cause of Dravet syndrome. In this study, we investigated genetic modifiers of this syndrome. We performed a mutational analysis of all coding exons of CACNA1A in 48 subjects with Dravet syndrome. To assess the effects of CACNA1A variants on the epileptic phenotypes of Dravet syndrome, we compared clinical features in two genotype groups: 1) subjects harboring SCN1A mutations but no CACNA1A variants (n=20) and 2) subjects with SCN1A mutations plus CACNA1A variants (n=20). CACNA1A variants detected in patients were studied using heterologous expression of recombinant human Ca(v)2.1 in HEK 293 cells and whole-cell patch-clamp recording. Nine CACNA1A variants, including six novel ones, were detected in 21 of the 48 subjects (43.8%). Based on the incidence of variants in healthy controls, most of the variants seemed to be common polymorphisms. However, the subjects harboring SCN1A mutations and CACNA1A variants had absence seizures more frequently than the patients with only SCN1A mutations (8/20 vs. 0/20, p=0.002). Moreover, the former group of subjects exhibited earlier onset of seizures and more frequent prolonged seizures before one year of age, compared to the latter group of subjects. The electrophysiological properties of four of the five novel Ca(v)2.1 variants exhibited biophysical changes consistent with gain-of-function. We conclude that CACNA1A variants in some persons with Dravet syndrome may modify the epileptic phenotypes.
備考
CACNA1A variants contribute to severity of seizures in Dravet syndrome
発行日
2013-02
出版物タイトル
Neurobiology of disease
50巻
出版者
Academic Press
開始ページ
209
終了ページ
217
ISSN
09699961
NCID
AA11645502
資料タイプ
学術雑誌論文
言語
English
OAI-PMH Set
岡山大学
論文のバージョン
author
PubMed ID
DOI
Web of Sience KeyUT
関連URL
isVersionOf https://doi.org/10.1016/j.nbd.2012.10.016
Citation
Iori Ohmori, Mamoru Ouchida, Katsuhiro Kobayashi, Yoshimi Jitsumori, Akiko Mori, Hiroyuki Michiue, Teiichi Nishiki, Yoko Ohtsuka, Hideki Matsui, CACNA1A variants may modify the epileptic phenotype of Dravet syndrome, Neurobiology of Disease, Volume 50, 2013, Pages 209-217, ISSN 0969-9961, https://doi.org/10.1016/j.nbd.2012.10.016.
助成機関名
文部科学省
助成番号
21390312