Simona Petrucci1,2, Monia Ginevrino3,4, Ilaria Trezzi5,6, Edoardo Monfrini5,6, Lucia Ricciardi7, Alberto Albanese8, Micol Avenali9,10, Paolo Barone11, Anna Rita Bentivoglio3,12, Vincenzo Bonifati13, Francesco Bove3,12, Laura Bonanni14, Livia Brusa15, Cristina Cereda9, Giovanni Cossu16, Chiara Criscuolo17, Giovanna Dati11, Anna De Rosa17, Roberto Eleopra18, Giovanni Fabbrini1,19,20, Laura Fadda21, Manuela Garbellini5,6, Brigida Minafra9, Marco Onofrj14, Claudio Pacchetti9, Ilaria Palmieri9,22, Maria Teresa Pellecchia11, Martina Petracca3,12, Marina Picillo11, Antonio Pisani23, Annamaria Vallelunga11, Roberta Zangaglia9, Alessio Di Fonzo5,6, Francesca Morgante7,24, Enza Maria Valente9,22. 1. Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy. 2. Department of Clinical and Molecular Medicine, S. Andrea University Hospital, Rome, Italy. 3. Agostino Gemelli IRCCS University Hospital Foundation, Rome, Italy. 4. Institute of Genomic Medicine, Catholic University, Rome, Italy. 5. Foundation IRCCS Ca'Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, Italy. 6. Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. 7. Neurosciences Research Centre, Molecular and Clinical Sciences Institute, St George's University of London, London, United Kingdom. 8. Department of Neurology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. 9. IRCCS Mondino Foundation, Pavia, Italy. 10. Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy. 11. Center for Neurodegenerative Diseases, Department of Medicine, Surgery and Dentistry "ScuolaMedicaSalernitana," University of Salerno, Baronissi, SA, Italy. 12. Institute of Neurology, Università Cattolica del Sacro Cuore, Rome, Italy. 13. Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. 14. Department of Neuroscience, Imaging and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy. 15. Parkinson Center, Neurology Complex Operative Unit, Sant'Eugenio Hospital, Rome, Italy. 16. Brotzu Hospital, Neurology, Cagliari, Italy. 17. Department of Neuroscience, Reproductive, and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy. 18. Parkinson and Movement Disorders Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. 19. Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy. 20. IRCCS Neuromed, Pozzilli (Isernia), Italy. 21. Department of Neurology, University Hospital of Cagliari, Cagliari, Italy. 22. Department of Molecular Medicine, University of Pavia, Pavia, Italy. 23. Department of Systems Medicine, University of Roma Tor Vergata, Rome, Italy. 24. Department of Experimental and Clinical Medicine, University of Messina, Messina, Italy.
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.
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.
Authors: Junchao Shen; Noor Amari; Rebecca Zack; R Tyler Skrinak; Travis L Unger; Marijan Posavi; Thomas F Tropea; Sharon X Xie; Vivianna M Van Deerlin; Richard B Dewey; Daniel Weintraub; John Q Trojanowski; Alice S Chen-Plotkin Journal: Ann Neurol Date: 2022-06-07 Impact factor: 11.274