The mutation spectrum of Parkinson‐disease‐related genes in early‐onset Parkinson's disease in ethnic Chinese

• DOI: 10.1111/ene.15509
• Publication Date: 2022-07-21T12:04:43Z
• Authors: Yong‐Ping Chen; Shi‐Hui Yu; Guo‐Hui Zhang; Yan‐Bing Hou; Xiao‐Jing Gu; Ru‐Wei Ou; Ying Shen; Wei Song; Xue‐Ping Chen; Bi Zhao; Bei Cao; Ling‐Yu Zhang; Ming‐Ming Sun; Fei‐Fei Liu; Qian‐Qian Wei; Kun‐Cheng Liu; Jun‐Yu Lin; Tian‐Mi Yang; Jing Yang; Ying Wu; Zheng Jiang; Jiao Liu; Yang‐Fan Cheng; Yi Xiao; Wei‐Ming Su; Fei Feng; Ying‐Ying Cai; Shi‐Rong Li; Tao Hu; Xiao‐Qin Yuan; Qing‐Qing Zhou; Na Shao; Sha Ma; Hui‐Fang Shang
• Keywords: Human genetics

Recent genetic progress has shown many causative/risk genes linked to Parkinson's disease (PD), mainly in patients of European ancestry. The study aimed investigate the PD-related and determine mutational spectrum early-onset PD ethnic Chinese.In this study, whole-exome sequencing and/or gene dosage analysis were performed 704 (EOPD) (onset age ≤45 years) 1866 controls. Twenty-six 20 other neurodegenerative lysosome diseases analysed.Eighty-two (11.6%, 82/704) EOPD carrying rare pathogenic/likely pathogenic variants identified. mutation frequency autosomal recessive inheritance (42.9%, 27/63) was much higher than that dominant (0.9%, 12/110) or sporadic (8.1%, 43/531). Bi-allelic mutations PRKN most frequent, accounting for 5.1% cases. Three common variants, p.A53V SNCA, p.G284R p.P53Afs*38 CHCHD2, occur exclusively Asians. putative damaging from GBA, PRKN, DJ1, PLA2G6 GCH1 contributed collective risk EOPD. Notably, protein-truncating CHCHD2 enriched EOPD, especially p.P53Afs*38, which also found three an independent cohort with late-onset (n = 1300). Functional experiments confirmed truncated cause loss function are mitochondrial dysfunction.Our reveals Chinese, may help develop scanning strategies, provided more evidence supporting PD.