Abstract

OBJECTIVE: To examine the genetic variability of Estonian Parkinson´s disease (PD) patients using an ongoing epidemiological study in combination with a genetic analysis. METHODS: This study was a community-based genetic screening study of 189 PD patients and 158 age and sex matched controls screened for potential mutations in 9 PD genes using next-generation sequencing and multiplex ligation-dependent probe amplification method. Different clinimetric scales and questionnaires were used to examine PD patients and assess clinical characteristics and severity of the disease. RESULTS: The overall frequency of pathogenic PD-causing variants was 1.1% (2/189), any rare genetic variant was present in 21.2% (40/189) of the patients and in 8.2% (13/158) of the controls (p<0.05). Variants of unknown significance accounted for 10.6% (20/189). Frequency of any GBA variant among PD patients was 10.1% (19/189) and in controls 3.8% (6/158). The frequency of any GBA variant in PD compared to controls was significantly higher (p = 0.035; OR 2.82; CI 95% 1.05-8.87). Burden of rare variants was not different between patients and controls. Also, a novel GBA pathogenic variant p.E10X was detected. CONCLUSION: Among different genetic variants identified in Estonian PD patients, GBA variants are the most common while an overall pathogenic variant frequency was 1.1%.