Background: Variants in GBA are 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 of GBA-related PD in Italy and correlated GBA variants with motor and nonmotor features and their occurrence over time. Methods: Sanger sequencing of the whole GBA gene was performed. Variants were classified as mild, severe, complex, and risk. β-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 β-glucocerebrosidase activity. Conclusions: GBA-PD is highly prevalent in Italy. Different types of mutations underlie distinct phenotypic profiles.

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Movement Disorders
Erasmus MC: University Medical Center Rotterdam

Petrucci, S. (Simona), Ginevrino, M. (Monia), Trezzi, I. (Ilaria), Monfrini, E. (Edoardo), Ricciardi, L. (Lucia), Albanese, A, … Valente, E.M. (Enza Maria). (2020). GBA-Related Parkinson's Disease: Dissection of Genotype–Phenotype Correlates in a Large Italian Cohort. Movement Disorders. doi:10.1002/mds.28195