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

Dissection Genotype Glucosylceramidase / genetics Humans Italy / epidemiology Mutation / genetics Parkinson Disease / epidemiology Phenotype

GBA Parkinson's disease dementia genotype-phenotype correlates impulsive-compulsive behavior

Journal

Movement disorders : official journal of the Movement Disorder Society

ISSN: 1531-8257

Titre abrégé: Mov Disord

Pays: United States

ID NLM: 8610688

Informations de publication

Date de publication:
11 2020

Historique:

received: 02 04 2020

revised: 17 05 2020

accepted: 03 06 2020

pubmed: 14 7 2020

medline: 28 4 2021

entrez: 14 7 2020

Statut: ppublish

Résumé

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. We determined the frequency of GBA-related PD in Italy and correlated GBA variants with motor and nonmotor features and their occurrence over time. 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. 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. GBA-PD is highly prevalent in Italy. Different types of mutations underlie distinct phenotypic profiles. © 2020 International Parkinson and Movement Disorder Society.

Sections du résumé

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

Identifiants

DOI: 10.1002/mds.28195 PMID: 32658388

pubmed: 32658388

doi: 10.1002/mds.28195

doi:

Substances chimiques

Glucosylceramidase EC 3.2.1.45

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

2106-2111

Investigateurs

Maria Concetta Altavista (MC)

Marianna Amboni (M)

Gianluca Ardolino (G)

Alfredo Berardelli (A)

Filippo Cogiamanian (F)

Carlo Colosimo (C)

Danilo Costanti (D)

Giuseppe De Michele (G)

Carlo Di Bonaventura (CD)

Giulia Di Lazzaro (G)

Vincenzo Di Lazzaro (V)

Antonio Emanuele Elia (A)

Roberto Erro (R)

Gina Ferrazzano (G)

Andrea Guerra (A)

Tamara Ialongo (T)

Maria Chiara Malaguti (MC)

Marta Melis (M)

Elena Moro (E)

Valentina Oppo (V)

Donatella Ottaviani (D)

Silvio Peluso (S)

Maria Luisa Quadri (ML)

Luigi Michele Romito (LM)

Marianna Sarchioto (M)

Tommaso Schirinzi (T)

Chiara Sorbera (C)

Alessandro Stefani (A)

Astrid Thomas (A)

Maria Luisa Valente (ML)

Giampiero Volpe (G)

Informations de copyright

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