Retrospective investigation of the relationship between GBA1 (Glucosylseramidase beta) gene variants and parkinson's disease

Parkinson's disease is the second common neurodegenerative disease characterized by tremor, rigidity and bradykinesia, with 0,5-1% prevalence of 60-65 years of age. The prevalence of ≥80 years of age increases to 1-3%. It is observed more common in men. Cardinal features of the disease are manifested by the loss of nigrostriatal dopaminergic neurons. While the definitive diagnosis is made by pathological examination, clinical diagnostic criteria are used in routine diagnosis. Its etiology is due to the complex interaction of environmental and genetic factors. Although it is largely idiopathic, 10-15% consists of familial form and 5-10% consists of monogenic form. It has shown that the biggest genetic risk factor is alterations in the GBA1 gene. In our study, clinical and genotypic data obtained by next generation sequencing targeted panel analysis of 40 Parkinson's patients were retrospectively examined: 7 different GBA1 gene variants were detected in 8 patients (20%) and disease-causing alterations in other genes associated with Parkinson's Disease (PINK1, LRRK2, PRKN, PLA2G6) in 4 patients (10%). 5 of the detected GBA1 gene variants (N409S, T408M, S310G, V499L, [D448H; H294Q]) has previously been reported in the literature in Parkinson's disease patients; 2 of them (A308T, c.533del) have not been previously reported in Parkinson's disease patients. Among our patients, the frequency of cognitive impairment in patients with GBA1 variant carrier (50%) was significantly higher than in those who did not carry it (9,1%) (p=0,029); It was observed that 2 groups had similar averages in terms of other clinical features and age of disease onset. Detection of GBA1 gene variants in Parkinson's disease patients and elucidation of genotype-phenotype correlations may provide significant gains for predicting prognosis in clinical follow-up of patients and may contribute to the identification of candidate patients for targeted therapies whose clinical trials are ongoing. This study is one of the rare studies examining GBA1 gene variants in Parkinson's disease patients in our country, and the diversity of GBA1 gene variants we detected despite the small sample size reveals the need for further studies in this area in the Turkish population.