Gba-Relatedparkinson'S Disease: Dissection Of Genotype-Phenotype Correlates In A Large Italian Cohort

Background Variants inGBAare the most common genetic risk factor for Parkinson's disease (PD). The impact of different variants on the PD clinical spectrum is still unclear. Objectives We determined the frequency ofGBA-related PD in Italy and correlatedGBAvariants with motor and nonmotor features and their occurrence over time. Methods Sanger sequencing of the wholeGBAgene was performed. Variants were classified as mild, severe, complex, and risk. beta-glucocerebrosidase activity was measured. The Kaplan-Meier method and Cox proportional hazard regression models were performed. Results Among 874 patients with PD, 36 variants were detected in 14.3%, including 20.4% early onset. Patients with GBA-PD had earlier and more frequent occurrence of several nonmotor symptoms. Patients with severe and complex GBA-PD had the highest burden of symptoms and a higher risk of hallucinations and cognitive impairment. Complex GBA-PD had the lowest beta-glucocerebrosidase activity. Conclusions GBA-PD is highly prevalent in Italy. Different types of mutations underlie distinct phenotypic profiles. (c) 2020 International Parkinson and Movement Disorder Society