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.

GBA-Related Parkinson's Disease: Dissection of Genotype–Phenotype Correlates in a Large Italian Cohort

Bonanni L.;Onofrj M.;Thomas A
2020

Abstract

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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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11564/733943
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