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

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...