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GBA ‐Related Parkinson's Disease: Dissection of Genotype–Phenotype Correlates in a Large Italian Cohort
Author(s) -
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
Publication year - 2020
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.28195
Subject(s) - glucocerebrosidase , parkinson's disease , proportional hazards model , disease , cohort , genotype , logistic regression , hazard ratio , medicine , oncology , psychology , genetics , gene , biology , confidence interval
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