オオヤマ　ゲンコウ   OYAMA Genko   大山　彦光    所属   埼玉医科大学  医学部 脳神経内科    職種   教授
論文種別	学術雑誌(原著)
言語種別	英語
査読の有無	査読あり
表題	Clinical characterization of patients with leucine-rich repeat kinase 2 genetic variants in Japan.
掲載誌名	正式名：Journal of human genetics
掲載区分	国外
巻・号・頁	65(9),771-781頁
著者・共著者	Yuanzhe Li,Aya Ikeda,Hiroyo Yoshino,Genko Oyama,Mitsuhiro Kitani,Kensuke Daida,Arisa Hayashida,Kotaro Ogaki,Kousuke Yoshida,Takashi Kimura,Yoshiaki Nakayama,Hidefumi Ito,Naoto Sugeno,Masashi Aoki,Hiroaki Miyajima,Katsuo Kimura,Naohisa Ueda,Masao Watanabe,Takao Urabe,Masashi Takanashi,Manabu Funayama,Kenya Nishioka,Nobutaka Hattori
発行年月	2020/05/13
概要	Variants of leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of familial Parkinson's disease (PD). We aimed to investigate the genetic and clinical features of patients with PD and LRRK2 variants in Japan by screening for LRRK2 variants in three exons (31, 41, and 48), which include the following pathogenic mutations: p.R1441C, p.R1441G, p.R1441H, p.G2019S, and p.I2020T. Herein, we obtained data containing LRRK2 variants derived from 1402 patients with PD (653 with sporadic PD and 749 with familial PD). As a result, we successfully detected pathogenic variants (four with p.R1441G, five with p.R1441H, seven with p.G2019S, and seven with p.I2020T) and other rare variants (two with p.V1447M, one with p.V1450I, one with p.T1491delT, and one with p.H2391Q). Two risk variants, p.P1446L and p.G2385R, were found in 10 and 146 patients, respectively. Most of the patients presented the symptoms resembling a common type of PD, such as middle-aged onset, tremor, akinesia, rigidity, and gait disturbance. Dysautonomia, cognitive decline, and psychosis were rarely observed. Each known pathogenic variant had a different founder in our cohort proven by haplotype analysis. The generation study revealed that the LRRK2 variants p.G2019S and p.I2020T were derived 3500 and 1300 years ago, respectively. Our findings present overviews of the prevalence and distribution of LRRK2 variants in Japanese cohorts.
DOI	10.1038/s10038-020-0772-4
PMID	32398759