論文

査読有り 国際誌
2020年5月13日

Clinical characterization of patients with leucine-rich repeat kinase 2 genetic variants in Japan.

Journal of human genetics
  • 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

記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s10038-020-0772-4

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.

リンク情報
DOI
https://doi.org/10.1038/s10038-020-0772-4
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32398759

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