GBA‐Related Parkinson's Disease: Dissection of Genotype–Phenotype Correlates in a Large Italian Cohort. Issue 11 (13th July 2020)

• Record Type: Journal Article
• Authors: Petrucci, Simona; Ginevrino, Monia; Trezzi, Ilaria; Monfrini, Edoardo; Ricciardi, Lucia; Albanese, Alberto; Avenali, Micol; Barone, Paolo; Bentivoglio, Anna Rita; Bonifati, Vincenzo; Bove, Francesco; Bonanni, Laura; Brusa, Livia; Cereda, Cristina; Cossu, Giovanni; Criscuolo, Chiara; Dati, Giovanna; De Rosa, Anna; Eleopra, Roberto; Fabbrini, Giovanni; Fadda, Laura; Garbellini, Manuela; Minafra, Brigida; Onofrj, Marco; Pacchetti, Claudio; Palmieri, Ilaria; Pellecchia, Maria Teresa; Petracca, Martina; Picillo, Marina; Pisani, Antonio; Vallelunga, Annamaria; Zangaglia, Roberta; Di Fonzo, Alessio; Morgante, Francesca; Valente, Enza Maria;
• Other Names: Altavista Maria Concetta investigator.; Amboni Marianna investigator.; Ardolino Gianluca investigator.; Berardelli Alfredo investigator.; Cogiamanian Filippo investigator.; Colosimo Carlo investigator.; Costanti Danilo investigator.; De Michele Giuseppe investigator.; Bonaventura Carlo Di investigator.; Di Lazzaro Giulia investigator.; Di Lazzaro Vincenzo investigator.; Emanuele Elia Antonio investigator.; Erro Roberto investigator.; Ferrazzano Gina investigator.; Guerra Andrea investigator.; Ialongo Tamara investigator.; Malaguti Maria Chiara investigator.; Melis Marta investigator.; Moro Elena investigator.; Oppo Valentina investigator.; Ottaviani Donatella investigator.; Peluso Silvio investigator.; Quadri Maria Luisa investigator.; Romito Luigi Michele investigator.; Sarchioto Marianna investigator.; Schirinzi Tommaso investigator.; Sorbera Chiara investigator.; Stefani Alessandro investigator.; Thomas Astrid investigator.; Valente Maria Luisa investigator.; Volpe Giampiero investigator.;
• Is Part Of: Movement disorders. Volume 35:Issue 11(2020)
• Page Start: 2106
• Page End: 2111
• Publication Date: 2020-07-13
• Subjects: dementia -- GBA -- genotype–phenotype correlates -- impulsive–compulsive behavior -- Parkinson's disease; Movement disorders -- Periodicals; 610
• DOI: 10.1002/mds.28195
• Languages: English
• ISSNs: 0885-3185

Abstract

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. © 2020 International Parkinson and Movement Disorder Society