Whole-exome sequencing in early-onset Parkinson's disease among ethnic Chinese.

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. • 18 patients (7.5%) carried pathogenic or likely pathogenic variants in known PD genes. • (Likely) pathogenic variants in Parkin and PINK1 were responsible for 4.2% of the patients. • Rare likely pathogenic variants in LRRK2 (1.7%) also appeared to be a relatively common cause of EOPD. • 7.5% of patients carried risk variants in either LRRK2 or GBA. [ABSTRACT FROM AUTHOR]