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Clinical characterization of patients with leucine-rich repeat kinase 2 genetic variants in Japan.
Journal of Human Genetics ( IF 2.6 ) Pub Date : 2020-05-13 , DOI: 10.1038/s10038-020-0772-4
Yuanzhe Li 1 , Aya Ikeda 1 , Hiroyo Yoshino 2 , Genko Oyama 1 , Mitsuhiro Kitani 3 , Kensuke Daida 1 , Arisa Hayashida 1 , Kotaro Ogaki 1 , Kousuke Yoshida 4 , Takashi Kimura 4 , Yoshiaki Nakayama 5 , Hidefumi Ito 5 , Naoto Sugeno 6 , Masashi Aoki 6 , Hiroaki Miyajima 7 , Katsuo Kimura 8 , Naohisa Ueda 8 , Masao Watanabe 9 , Takao Urabe 9 , Masashi Takanashi 1 , Manabu Funayama 1, 2 , Kenya Nishioka 1 , Nobutaka Hattori 1, 2
Affiliation  

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.

中文翻译:

日本富含亮氨酸重复激酶 2 基因变异患者的临床特征。

富含亮氨酸重复激酶 2 (LRRK2) 的变体是家族性帕金森病 (PD) 最常见的遗传原因。我们旨在通过筛选三个外显子(31、41 和 48)中的 LRRK2 变异来研究日本 PD 和 LRRK2 变异患者的遗传和临床特征,其中包括以下致病突变:p.R1441C、p.R1441G、 p.R1441H、p.G2019S 和 p.I2020T。在这里,我们获得了包含来自 1402 名 PD 患者(653 名散发性 PD 和 749 名家族性 PD)的 LRRK2 变体的数据。结果,我们成功地检测到了致病变异(4 个带有 p.R1441G,5 个带有 p.R1441H,7 个带有 p.G2019S,7 个带有 p.I2020T)和其他罕见变异(两个带有 p.V1447M,一个带有 p. V1450I,一个带有 p.T1491delT,一个带有 p.H2391Q)。两个风险变体,p.P1446L 和 p.G2385R,分别在 10 名和 146 名患者中发现。大部分患者出现类似PD常见类型的症状,如中年发病、震颤、运动不能、强直和步态障碍。很少观察到自主神经失调、认知能力下降和精神病。通过单倍型分析证明,在我们的队列中,每个已知的致病变异都有不同的创始人。世代研究表明,LRRK2 变体 p.G2019S 和 p.I2020T 分别起源于 3500 年和 1300 年前。我们的研究结果概述了日本队列中 LRRK2 变体的流行和分布。通过单倍型分析证明,在我们的队列中,每个已知的致病变异都有不同的创始人。世代研究表明,LRRK2 变体 p.G2019S 和 p.I2020T 分别起源于 3500 年和 1300 年前。我们的研究结果概述了日本队列中 LRRK2 变体的流行和分布。通过单倍型分析证明,在我们的队列中,每个已知的致病变异都有不同的创始人。世代研究表明,LRRK2 变体 p.G2019S 和 p.I2020T 分别起源于 3500 年和 1300 年前。我们的研究结果概述了日本队列中 LRRK2 变体的流行和分布。
更新日期:2020-05-13
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