Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Internal Medicine, Wangjiang Hospital, Sichuan University, Chengdu, Sichuan, China.
Neurobiol Aging. 2020 Jun;90:150.e5-150.e11. doi: 10.1016/j.neurobiolaging.2019.12.023. Epub 2020 Jan 7.
Although early-onset Parkinson's disease (EOPD) has a more penetrant genetic etiology, the genetic architecture of EOPD remains unclear. The objectives of this study were to assess the genetic and clinical features of EOPD among ethnic Chinese from mainland China. Using whole-exome sequencing, we performed genetic analyses of 240 participants including 193 with sporadic and 47 with familial EOPD (age of onset <50 years). In total, 18 patients (7.5%) harbored pathogenic or likely pathogenic variants in known PD genes. Among these variants, biallelic variants in Parkin and PINK1 were responsible for 4.2% of cases, and rare likely pathogenic variants in LRRK2 (1.7%) also appeared to be a relatively common cause of EOPD. Notably, 7.5% of patients carried risk variants in either LRRK2 or GBA, which should also be considered for EOPD. Nevertheless, 41 patients (17.1%) had rare variants of unknown significance. In conclusion, our findings provide a better understanding of the genetic architecture of PD among ethnic Chinese, and the pathogenicity of numerous rare variants should be further investigated.
尽管早发性帕金森病 (EOPD) 具有更强的遗传病因学，但 EOPD 的遗传结构仍不清楚。本研究的目的是评估中国大陆汉族人群中 EOPD 的遗传和临床特征。我们使用全外显子组测序对 240 名参与者进行了遗传分析，其中 193 名患有散发性 EOPD（发病年龄<50 岁），47 名患有家族性 EOPD（发病年龄<50 岁）。总共有 18 名患者（7.5%）携带已知 PD 基因中的致病性或可能致病性变异。在这些变异中，Parkin 和 PINK1 的双等位基因变异导致 4.2%的病例，LRRK2 中的罕见可能致病性变异（1.7%）似乎也是 EOPD 的一个相对常见原因。值得注意的是，7.5%的患者携带 LRRK2 或 GBA 中的风险变异，这也应考虑用于 EOPD。然而，41 名患者（17.1%）携带意义不明的罕见变异。总之，我们的研究结果提供了对汉族人群中 PD 遗传结构的更好理解，并且许多罕见变异的致病性应进一步研究。
