ミウラ　マズミ   Mazumi Miura   三浦　真澄    所属   川崎医科大学  医学部 臨床医学　小児科学    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	De novo ATP1A3 variants cause polymicrogyria.
掲載誌名	正式名：Science advances
掲載区分	国外
巻・号・頁	7(13)
著者・共著者	Satoko Miyatake,Mitsuhiro Kato,Takuma Kumamoto,Tomonori Hirose,Eriko Koshimizu,Takaaki Matsui,Hideyuki Takeuchi,Hiroshi Doi,Keisuke Hamada,Mitsuko Nakashima,Kazunori Sasaki,Akio Yamashita,Atsushi Takata,Kohei Hamanaka,Mai Satoh,Takabumi Miyama,Yuri Sonoda,Momoko Sasazuki,Hiroyuki Torisu,Toshiro Hara,Yasunari Sakai,Yushi Noguchi,Mazumi Miura,Yoko Nishimura,Kazuyuki Nakamura,Hideyuki Asai,Nodoka Hinokuma,Fuyuki Miya,Tatsuhiko Tsunoda,Masami Togawa,Yukihiro Ikeda,Nobusuke Kimura,Kaoru Amemiya,Asako Horino,Masataka Fukuoka,Hiroko Ikeda,Goni Merhav,Nina Ekhilevitch,Masaki Miura,Takeshi Mizuguchi,Noriko Miyake,Atsushi Suzuki,Shouichi Ohga,Hirotomo Saitsu,Hidehisa Takahashi,Fumiaki Tanaka,Kazuhiro Ogata,Chiaki Ohtaka-Maruyama,Naomichi Matsumoto
発行年月	2021/03
概要	Polymicrogyria is a common malformation of cortical development whose etiology remains elusive. We conducted whole-exome sequencing for 124 patients with polymicrogyria and identified de novo ATP1A3 variants in eight patients. Mutated ATP1A3 causes functional brain diseases, including alternating hemiplegia of childhood (AHC), rapid-onset dystonia parkinsonism (RDP), and cerebellar ataxia, areflexia, pes cavus, optic nerve atrophy, and sensorineural deafness (CAPOS). However, our patients showed no clinical features of AHC, RDP, or CAPOS and had a completely different phenotype: a severe form of polymicrogyria with epilepsy and developmental delay. Detected variants had different locations in ATP1A3 and different functional properties compared with AHC-, RDP-, or CAPOS-associated variants. In the developing cerebral cortex of mice, radial neuronal migration was impaired in neurons overexpressing the ATP1A3 variant of the most severe patients, suggesting that this variant is involved in cortical malformation pathogenesis. We propose a previously unidentified category of polymicrogyria associated with ATP1A3 abnormalities.
DOI	10.1126/sciadv.abd2368
PMID	33762331