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

Petrucci, S.; Ginevrino, M.; Trezzi, I.; Monfrini, E.; Ricciardi, L.; Albanese, A.; Avenali, M.; Barone, P.; Bentivoglio, A. R.; Bonifati, V.; Bove, F.; Bonanni, L.; Brusa, L.; Cereda, C.; Cossu, G.; Criscuolo, C.; Dati, G.; De Rosa, A.; Eleopra, R.; Fabbrini, G.; Fadda, L.; Garbellini, M.; Minafra, B.; Onofrj, M.; Pacchetti, C.; Palmieri, I.; Pellecchia, M. T.; Petracca, M.; Picillo, M.; Pisani, A.; Vallelunga, A.; Zangaglia, R.; Di Fonzo, A.; Morgante, F.; Valente, E. M.; Altavista, M. C.; Amboni, M.; Ardolino, G.; Berardelli, A.; Cogiamanian, F.; Colosimo, C.; Costanti, D.; De Michele, G.; Bonaventura, C. D.; Di Lazzaro, G.; Di Lazzaro, V.; Emanuele Elia, A.; Erro, R.; Ferrazzano, G.; Guerra, A.; Ialongo, T.; Malaguti, M. C.; Melis, M.; Moro, E.; Oppo, V.; Ottaviani, D.; Peluso, S.; Quadri, M. L.; Romito, L. M.; Sarchioto, M.; Schirinzi, T.; Sorbera, C.; Stefani, A.; Thomas, A.; Valente, M. L.; Volpe, G; ITA-GENE-PD Study, Group.

doi:10.1002/mds.28195

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. © 2020 International Parkinson and Movement Disorder Society.

GBA-Related Parkinson's Disease: Dissection of Genotype–Phenotype Correlates in a Large Italian Cohort / Petrucci, S.; Ginevrino, M.; Trezzi, I.; Monfrini, E.; Ricciardi, L.; Albanese, A.; Avenali, M.; Barone, P.; Bentivoglio, A. R.; Bonifati, V.; Bove, F.; Bonanni, L.; Brusa, L.; Cereda, C.; Cossu, G.; Criscuolo, C.; Dati, G.; De Rosa, A.; Eleopra, R.; Fabbrini, G.; Fadda, L.; Garbellini, M.; Minafra, B.; Onofrj, M.; Pacchetti, C.; Palmieri, I.; Pellecchia, M. T.; Petracca, M.; Picillo, M.; Pisani, A.; Vallelunga, A.; Zangaglia, R.; Di Fonzo, A.; Morgante, F.; Valente, E. M.; Altavista, M. C.; Amboni, M.; Ardolino, G.; Berardelli, A.; Cogiamanian, F.; Colosimo, C.; Costanti, D.; De Michele, G.; Bonaventura, C. D.; Di Lazzaro, G.; Di Lazzaro, V.; Emanuele Elia, A.; Erro, R.; Ferrazzano, G.; Guerra, A.; Ialongo, T.; Malaguti, M. C.; Melis, M.; Moro, E.; Oppo, V.; Ottaviani, D.; Peluso, S.; Quadri, M. L.; Romito, L. M.; Sarchioto, M.; Schirinzi, T.; Sorbera, C.; Stefani, A.; Thomas, A.; Valente, M. L.; Volpe, G; ITA-GENE-PD Study, Group.. - In: MOVEMENT DISORDERS. - ISSN 0885-3185. - 35:11(2020), pp. 2106-2111. [10.1002/mds.28195]