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

Title: GBA‐Related Parkinson's Disease: Dissection of Genotype–Phenotype Correlates in a Large Italian Cohort
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
Contributors: Italian Ministry of Health; Stichting Parkinson Fonds, The Netherlands
Source: Movement Disorders ; volume 35, issue 11, page 2106-2111 ; ISSN 0885-3185 1531-8257
Publisher Information: Wiley
Publication Year: 2020
Collection: Wiley Online Library (Open Access Articles via Crossref)
Description: 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
Document Type: article in journal/newspaper
Language: English
DOI: 10.1002/mds.28195
Availability: https://doi.org/10.1002/mds.28195; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fmds.28195; https://onlinelibrary.wiley.com/doi/pdf/10.1002/mds.28195; https://onlinelibrary.wiley.com/doi/full-xml/10.1002/mds.28195
Rights: http://onlinelibrary.wiley.com/termsAndConditions#vor
Accession Number: edsbas.E90C3651
Database: BASE