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. 2025 Jan;46(1):165-174.
doi: 10.1007/s10072-024-07690-7. Epub 2024 Jul 22.

Genetic mutations in Parkinson's disease: screening of a selected population from North-Eastern Italy

Giulia Bonato  1   2 , Angelo Antonini  1   2 , Francesca Pistonesi  1   2   3 , Marta Campagnolo  1   2 , Andrea Guerra  1   2 , Roberta Biundo  1   2   3 , Manuela Pilleri  4 , Cinzia Bertolin  5 , Leonardo Salviati  5 , Miryam Carecchio  6   7
Affiliations

Genetic mutations in Parkinson's disease: screening of a selected population from North-Eastern Italy

Giulia Bonato et al. Neurol Sci. 2025 Jan.

Abstract

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder with a multifactorial pathogenesis. Several genetic variants increase the risk of PD and about 5-10% of cases are monogenic. This study aims to define the genetic bases and clinical features of PD in a cohort of patients from Northeastern Italy, a peculiar geographical area previously not included in genetic screenings.

Methods: Using an NGS multigenic panel, 218 PD patients were tested based on age at onset, family history and development of atypical features.

Results: A total of 133 genetic variants were found in 103 patients. Monogenic PD was diagnosed in 43 patients (20% of the cohort); 28 (12.8%) carried mutations in GBA1, 10 in LRRK2 (4.6%) and 5 in PRKN (2.3%). In 17% of patients the genetic defect remained of uncertain interpretation. The selection criterion "age of onset < 55 years" was a significant predictor of a positive genetic test (OR 3.8, p 0.0037). GBA1 patients showed more severe symptoms and a higher burden of motor and non-motor complications compared to negative patients (dyskinesias OR 3, sleep disturbances OR 2.8, cognitive deficits OR 3.6; p < 0.05), with greater autonomic dysfunction (COMPASS-31 score 34.1 vs 20.2, p 0.03).

Conclusions: Applying simple clinical criteria for genetic testing allows to increase the probability to identify patients with monogenic PD and better allocate resources. This process is critical to widen the understanding of disease mechanisms and to increase the individuation of patients potentially benefitting from future disease-modifying therapies.

Keywords: GBA; Genetics; NGS; Parkinson.

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Conflict of interest statement

Declarations. Ethical approval: This research study was conducted retrospectively from data obtained for clinical purposes and it is an observational study. All procedures performed in the study are in accordance with the ethical standards of the University of Padova institutional research committee and with the 1964 Helsinki Declaration and its later amendments. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Informed consent: Consent was obtained from patients for all procedures as appropriately needed. Competing interests: The authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
A PD, parkinsonism and research genes found in the study: frequency and classification of the variants in each gene as pathogenic, VUS or benign according to ACMG classification; B Genetic spectrum of patients with a definite diagnosis of monogenic PD
Fig. 2
Fig. 2
Main clinical features of GBA1-PD patients compared to negative controls; * indicates statistically significant differences between the two groups
Fig. 3
Fig. 3
Results of cognitive assessment showing mean Z scores in the five cognitive domains in different genetic subgroups of patients (*indicates pathologic mean scores). The lower part of the image reports the percentage of patients with difficulties in the same cognitive domains
See this image and copyright information in PMC

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