Mutations in the genes of lysosomal storage diseases as a risk factor for the development of Parkinson’s disease

Introduction. The accumulation of neurotoxic forms of alpha-synuclein protein in brain tissues plays a key role in the pathogenesis of Parkinson’s disease (PD). In this case, lysosome dysfunction is considered as one of the possible causes of alpha-synuclein accumulation in cells. The commonality of the pathogenesis of PD and lysosomal storage diseases (LSD) is discussed. Mutations in two genes, GBA1 and SMPD1, leading to the development of Gaucher and Niemann-Pick А/В diseases, respectively, are associated with a high risk of PD development. The contribution of rare variants in other LSD genes is discussed.
The objective of this study was to assess the association of rare gene variants of lysosomal storage diseases and Parkinson’s disease in the North-Western region of Russia.
Methods and materials. An analysis of data obtained as a result of massive parallel sequencing of 44 genes associated with lysosomal storage diseases was carried out in 496 patients with PD and 401 individuals in the control group.
Results.The study revealed a statistically significant difference in the frequency of occurrence of pathogenic and likely pathogenic variants of the LSD genes among patients with PD compared to the control group (p<0.05). An association of pathogenic and opportunistic rare variants of the ARSA and SGSH genes with an increased risk of PD development was revealed.
Conclusion. The obtained data confirm the role of rare variants of the LSD genes in PD pathogenesis.

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