Analysis of mutations associated with Parkinson’s disease in patients of the Krasnoyarsk region

Background. Parkinson’s disease (PD) is one of the common neurodegenerative diseases. Several genes are known (SNCA, PARK2, PINK1, PARK7 (DJ-1) and LRRK2), mutations in which have a pathological significance in the development of monogenic PD; association with PD of other genes (for example, UCHL1, ATP13A2) requires further study. It is also known, that GBA gene is associated with an increased risk of PD developing.Aim. Analysis of mutations and polymorphisms in the PARK2, PINK1, SNCA, ATP13A2, PARK7, LRRK2, UCHL, GCH1 and GBA genes in patients with PD from Krasnoyarsk region.Material and methods. The 60 patients with sporadic and familial forms of PD were included in the study. The SALSA MLPA Holland P051 and P052 kits («MRC Amsterdam», The Netherlands) were used to detect deletions and duplications in the PARK2, PINK1, SNCA, ATP13A2, PARK7, LRRK2, UCHL, GCH1 genes, as well as point mutations A30P in the SNCA gene and G2019S in the LRRK2 gene. Analysis of the GBA gene was carried out by Senger sequencing.Results. None of the 60 patients had mutations that were searched with the SALSA MLPA Holland P051 and P052 kits. 6 different mutations in the GBA gene were found in 9 out of 60 patients with PD. L444P («severe» PD — associated mutation) — in two patients, D409H («severe» PD — associated mutation) — in one patient, T369M (polymorphism, possibly associated with PD) — in two patients, E326K (polymorphism, possibly associated with PD) — in one patient, V460V (synonymous variant, which is part of the composition of the complex RecNcil mutation (p.L444P; p.A456P; p.V460V) associated with PD) — in two patients and variant C.*92g>A (3’ — UTR polymorphism, possibly associated with PD) — in one patient. Two patients had compound heterozygous carriers of two variants.Conclusion. This paper presents the genetic analysis results of the PD associated genes among patients from the Krasnoyarsk region. No mutations were detected in the PARK2, PINK1, SNCA, ATP13A2, PARK7, LRRK2, UCHL and GCH1 genes. Genetic variants analysis of the GBA gene showed similar frequency in the patients from the Krasnoyarsk region as in European populations.