Objective: The objectives of this study were to assess the genetic and clinical features of early-onset Parkinson’s disease (EOPD) among ethnic Chinese from mainland China.

Background: Notably, patients with EOPD have a more penetrant genetic etiology than late-onset Parkinson’s disease and thus represent a good cohort to explore the genetics of PD. To date, there is still limited detailed data on the genetic architecture of EOPD in ethnic Chinese.

Method: Using whole-exome sequencing (WES), we performed genetic analyses of 240 participants including 193 with sporadic and 47 with familial EOPD (age of onset < 50 years) from the Movement Disorders Outpatient Clinic of West China Hospital, Sichuan University (Chengdu, China).

Results: In total, 18 patients (7.5%) harbored 24 pathogenic or likely pathogenic variants in the AR PD genes (Parkin, PINK1, PLA2G6, and SYNJ1) and the AD PD genes (LRRK2, SNCA, and CHCHD2). 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.

Conclusion: 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.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/whole-exome-sequencing-in-early-onset-parkinsons-disease-among-ethnic-chinese/