A Possible Modifying Effect of the G2019S Mutation in the LRRK2 Gene on GBA Parkinson's Disease

Background The phenotype of Parkinson's disease (PD) is milder among patients with LRRK2‐PD and more severe among patients with GBA‐PD; however, whether an additive phenotypical effect occurs among dual‐mutation carriers requires validation. Objective The objective of this study was to explore the phenotypic expression of patients with PD who carry mutations in both genes compared with a single‐mutation presentation. Methods Patients with PD were genotyped for the G2019S‐LRRK2 mutation and 9 mutations in the GBA gene. Subjects were classified into 5 groups: idiopathic PD, mild GBA‐PD, severe GBA‐PD, LRRK2‐PD, and LRRK2+GBA‐PD. Clinical symptoms were evaluated using performance‐based measures. Results A total of 1090 patients with idiopathic PD, 155 patients with LRRK2‐PD, 155 patients with mild GBA‐PD, 56 patients with severe GBA‐PD, and 27 patients with LRRK2+GBA‐PD participated in this study. The patients with LRRK2‐PD and LRRK2+GBA‐PD exhibited lower scores on total Unified Parkinson's Disease Rating Scale (P