The role of genetics in Parkinson’s disease: a large cohort study in Chinese mainland population

作者：Yuwen Zhao, Lixia Qin, Hongxu Pan, Zhenhua Liu, Jiang Li, Yan He, Qian Zeng, Xun Zhou, Xiaoxia Zhou, Yangjie Zhou, Zhenghuan Fang, Zheng Wang, Yaqin Xiang, Honglan Yang, Yige Wang, Kailin Zhang, Rui Zhang, Runcheng He, Xiaoting Zhou, Zhou Zhou, Nannan Yang, Dongxiao Liang, Juan Chen, Xuxiang Zhang, Yao Zhou, Hongli Liu, Penghui Deng, Kun Xu, Ke Xu, Chaojun Zhou, Junfei Zhong, Qian Xu, Qiying Sun, Bin Li, Guihu Zhao, Tao Wang, Ling Chen, Huifang Shang, Weiguo Liu, Piu Chan, Zheng Xue, Qing Wang, Li Guo, Xuejing Wang, Changshui Xu, Zhentao Zhang, Tao Chen, Lifang Lei, Hainan Zhang, Chunyu Wang, Jieqiong Tan, Xinxiang Yan, Lu Shen, Hong Jiang, Zhuohua Zhang, Zhengmao Hu, Kun Xia, Zhenyu Yue, Jinchen Li, Jifeng Guo, Beisha Tang · 发表于：Brain · 年份：2020 · DOI：10.1093/brain/awaa167 · 被引用次数：172 · 研究领域：Parkinson's Disease Mechanisms and Treatments、Neurological diseases and metabolism、RNA regulation and disease

This study aimed to determine the mutational spectrum of familial Parkinson's disease and sporadic early-onset Parkinson's disease (sEOPD) in a mainland Chinese population and the clinical features of mutation carriers. We performed multiplex ligation-dependent probe amplification assays and whole-exome sequencing for 1676 unrelated patients with Parkinson's disease in a mainland Chinese population, including 192 probands from families with autosomal-recessive Parkinson's disease, 242 probands from families with autosomal-dominant Parkinson's disease, and 1242 sEOPD patients (age at onset ≤ 50). According to standards and guidelines from the American College of Medical Genetics and Genomics, pathogenic/likely pathogenic variants in 23 known Parkinson's disease-associated genes occurred more frequently in the autosomal-recessive Parkinson's disease cohort (65 of 192, 33.85%) than in the autosomal-dominant Parkinson's disease cohort (10 of 242, 4.13%) and the sEOPD cohort (57 of 1242, 4.59%), which leads to an overall molecular diagnostic yield of 7.88% (132 of 1676). We found that PRKN was the most frequently mutated gene (n = 83, 4.95%) and present the first evidence of an SNCA duplication and LRRK2 p.N1437D variant in mainland China. In addition, several novel pathogenic/likely pathogenic variants including LRRK2 (p.V1447M and p.Y1645S), ATP13A2 (p.R735X and p.A819D), FBXO7 (p.G67E), LRP10 (c.322dupC/p.G109Rfs*51) and TMEM230 (c.429delT/p.P144Qfs*2) were identified in our co...