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

Simona Petrucci; Monia Ginevrino; Ilaria Trezzi; Edoardo Monfrini; Lucia Ricciardi; Alberto Albanese; Micol Avenali; Paolo Barone; Anna Rita Bentivoglio; Vincenzo Bonifati; Francesco Bove; Laura Bonanni; Livia Brusa; Cristina Cereda; Giovanni Cossu; Chiara Criscuolo; Giovanna Dati; Anna De Rosa; Roberto Eleopra; Giovanni Fabbrini; Laura Fadda; Manuela Garbellini; Brigida Minafra; Marco Onofrj; Claudio Pacchetti; Ilaria Palmieri; Maria Teresa Pellecchia; Martina Petracca; Marina Picillo; Antonio Pisani; Annamaria Vallelunga; Roberta Zangaglia; Alessio Di Fonzo; Francesca Morgante; Enza Maria Valente

doi:10.1002/mds.28195

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

Simona Petrucci, Monia Ginevrino, Ilaria Trezzi, Edoardo Monfrini, Lucia Ricciardi, Alberto Albanese, Micol Avenali, Paolo Barone, Anna Rita Bentivoglio, Vincenzo Bonifati, Francesco Bove, Laura Bonanni, Livia Brusa, Cristina Cereda, Giovanni Cossu, Chiara Criscuolo, Giovanna Dati, Anna De Rosa, Roberto Eleopra, Giovanni FabbriniLaura Fadda, Manuela Garbellini, Brigida Minafra, Marco Onofrj, Claudio Pacchetti, Ilaria Palmieri, Maria Teresa Pellecchia, Martina Petracca, Marina Picillo, Antonio Pisani, Annamaria Vallelunga, Roberta Zangaglia, Alessio Di Fonzo, Francesca Morgante, Enza Maria Valente

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	2106-1
Number of pages	6
Journal	Movement Disorders
Volume	35
Issue number	11
DOIs	https://doi.org/10.1002/mds.28195
Publication status	Published - Nov 13 2020

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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., ... Valente, E. M. (2020). GBA-Related Parkinson's Disease: Dissection of Genotype-Phenotype Correlates in a Large Italian Cohort. Movement Disorders, 35(11), 2106-1. https://doi.org/10.1002/mds.28195

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

In: Movement Disorders, Vol. 35, No. 11, 13.11.2020, p. 2106-1.

Research output: Contribution to journal › Article › peer-review

Petrucci, S, Ginevrino, M, Trezzi, I, Monfrini, E, Ricciardi, L, Albanese, A , Avenali, M, Barone, P, Bentivoglio, AR, 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, MT, Petracca, M, Picillo, M, Pisani, A, Vallelunga, A, Zangaglia, R , Di Fonzo, A, Morgante, F & Valente, EM 2020, 'GBA-Related Parkinson's Disease: Dissection of Genotype-Phenotype Correlates in a Large Italian Cohort', Movement Disorders, vol. 35, no. 11, pp. 2106-1. https://doi.org/10.1002/mds.28195

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. / GBA-Related Parkinson's Disease : Dissection of Genotype-Phenotype Correlates in a Large Italian Cohort. In: Movement Disorders. 2020 ; Vol. 35, No. 11. pp. 2106-1.

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title = "GBA-Related Parkinson's Disease: Dissection of Genotype-Phenotype Correlates in a Large Italian Cohort",

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. {\textcopyright} 2020 International Parkinson and Movement Disorder Society.",

author = "Simona Petrucci and Monia Ginevrino and Ilaria Trezzi and Edoardo Monfrini and Lucia Ricciardi and Alberto Albanese and Micol Avenali and Paolo Barone and Bentivoglio, {Anna Rita} and Vincenzo Bonifati and Francesco Bove and Laura Bonanni and Livia Brusa and Cristina Cereda and Giovanni Cossu and Chiara Criscuolo and Giovanna Dati and {De Rosa}, Anna and Roberto Eleopra and Giovanni Fabbrini and Laura Fadda and Manuela Garbellini and Brigida Minafra and Marco Onofrj and Claudio Pacchetti and Ilaria Palmieri and Pellecchia, {Maria Teresa} and Martina Petracca and Marina Picillo and Antonio Pisani and Annamaria Vallelunga and Roberta Zangaglia and {Di Fonzo}, Alessio and Francesca Morgante and Valente, {Enza Maria}",

note = "{\textcopyright} 2020 International Parkinson and Movement Disorder Society.",

year = "2020",

month = nov,

day = "13",

doi = "10.1002/mds.28195",

language = "English",

volume = "35",

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TY - JOUR

T1 - GBA-Related Parkinson's Disease

T2 - Dissection of Genotype-Phenotype Correlates in a Large Italian Cohort

AU - Petrucci, Simona

AU - Ginevrino, Monia

AU - Trezzi, Ilaria

AU - Monfrini, Edoardo

AU - Ricciardi, Lucia

AU - Albanese, Alberto

AU - Avenali, Micol

AU - Barone, Paolo

AU - Bentivoglio, Anna Rita

AU - Bonifati, Vincenzo

AU - Bove, Francesco

AU - Bonanni, Laura

AU - Brusa, Livia

AU - Cereda, Cristina

AU - Cossu, Giovanni

AU - Criscuolo, Chiara

AU - Dati, Giovanna

AU - De Rosa, Anna

AU - Eleopra, Roberto

AU - Fabbrini, Giovanni

AU - Fadda, Laura

AU - Garbellini, Manuela

AU - Minafra, Brigida

AU - Onofrj, Marco

AU - Pacchetti, Claudio

AU - Palmieri, Ilaria

AU - Pellecchia, Maria Teresa

AU - Petracca, Martina

AU - Picillo, Marina

AU - Pisani, Antonio

AU - Vallelunga, Annamaria

AU - Zangaglia, Roberta

AU - Di Fonzo, Alessio

AU - Morgante, Francesca

AU - Valente, Enza Maria

PY - 2020/11/13

Y1 - 2020/11/13

N2 - 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.

AB - 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.

U2 - 10.1002/mds.28195

DO - 10.1002/mds.28195

M3 - Article

C2 - 32658388

VL - 35

SP - 2106

EP - 2101

JO - Movement Disorders

JF - Movement Disorders

SN - 0885-3185

IS - 11

ER -