Analysis of ADORA2A, MTA1, PTGDS, PTGS2, NSF, and HNMT Gene Expression Levels in Peripheral Blood of Patients with Early Stages of Parkinson's Disease.

Parkinson's disease (PD) is a common chronic, age-related neurodegenerative disease. This disease is characterized by a long prodromal period. In this context, it is important to search for the genes and mechanisms that are involved in the development of the pathological process in the earliest stages of the disease. Published data suggest that blood cells, particularly lymphocytes, may be a model for studying the processes that occur in the brain in PD. Thus, in the present work, we performed an analysis of changes in the expression of the genes ADORA2A, MTA1, PTGDS, PTGS2, NSF, and HNMT in the peripheral blood of patients with early stages of PD (stages 1 and 2 of the Hoehn-Yahr scale). We found significant and PD-specific expression changes of four genes, i.e., MTA1, PTGS2, NSF, and HNMT, in the peripheral blood of patients with early stages of PD. These genes may be associated with PD pathogenesis in the early clinical stages and can be considered as potential candidate genes for this disease. Altered expression of the ADORA2A gene in treated PD patients may indicate that this gene is involved in processes affected by antiparkinsonian therapy.

The spectrum of SDHD mutations in Russian patients with head and neck paraganglioma.

AIM OF THE STUDY: It was found that the mutations in the SDHD gene, encoding one of subunits of the succinate dehydrogenase complex, lead to the development of head and neck paraganglioma (HNPGL). We analyzed this gene in 91 patients with HNPGL from Russia. MATERIALS AND METHODS: DNA was isolated from the whole blood. A screening for mutations was performed by Sanger sequencing. RESULTS: We revealed three missense mutations that have been described previously: p.Pro81Leu, p.His102Arg, p.Tyr114Cys. Moreover, we identified a novel potentially pathogenic variant (p.Trp105*). CONCLUSIONS: We found that mutations in the SDHD gene were less common in Russian patients compared with the majority of European populations. It was shown that the p.His102Arg mutation is a major mutation in Russia. We confirmed the previous suggestion that a bilateral localization of the tumor and the carotid type represent a marker of the genetically determined form of HNPGL.

Whole-Exome Sequencing in Searching for New Variants Associated With the Development of Parkinson's Disease.

Background: Parkinson's disease (PD) is a complex disease with its monogenic forms accounting for less than 10% of all cases. Whole-exome sequencing (WES) technology has been used successfully to find mutations in large families. However, because of the late onset of the disease, only small families and unrelated patients are usually available. WES conducted in such cases yields in a large number of candidate variants. There are currently a number of imperfect software tools that allow the pathogenicity of variants to be evaluated. Objectives: We analyzed 48 unrelated patients with an alleged autosomal dominant familial form of PD using WES and developed a strategy for selecting potential pathogenetically significant variants using almost all available bioinformatics resources for the analysis of exonic areas. Methods: DNA sequencing of 48 patients with excluded frequent mutations was performed using an Illumina HiSeq 2500 platform. The possible pathogenetic significance of identified variants and their involvement in the pathogenesis of PD was assessed using SNP and Variation Suite (SVS), Combined Annotation Dependent Depletion (CADD) and Rare Exome Variant Ensemble Learner (REVEL) software. Functional evaluation was performed using the Pathway Studio database. Results: A significant reduction in the search range from 7082 to 25 variants in 23 genes associated with PD or neuronal function was achieved. Eight (FXN, MFN2, MYOC, NPC1, PSEN1, RET, SCN3A and SPG7) were the most significant. Conclusions: The multistep approach developed made it possible to conduct an effective search for potential pathogenetically significant variants, presumably involved in the pathogenesis of PD. The data obtained need to be further verified experimentally.

Second mutation in PARK2 is absent in patients with sporadic Parkinson's disease and heterozygous exonic deletions/duplications in parkin gene.

AIM OF THE STUDY: Mutations in PARK2 are one of the causes of Parkinson's disease (PD). Deletions and duplications/triplications of one exon or exon groups account for a large proportion of mutations in the gene. At the present time, it is still not fully clear whether heterozygous mutations cause the development of PD. Our study aimed at conducting screening for mutations in PARK2 in patients with a sporadic form of PD to clarify the role of PARK2 in the development of PD. MATERIALS AND METHODS: The cohort of 327 patients with PD was screened by quantitative real-time polimerase chain reaction (PCR) with subsequent Sanger sequencing. RESULTS: It was found that a sufficiently large proportion of these patients (21 patients, 6.4%) were carriers of heterozygous deletions or duplications in PARK2. Analysis of PARK2 exon rearrangement carriers for the presence of point mutations in PARK2 did not reveal any variants with pathogenic significance. CONCLUSIONS: Thus, our data indicate that heterozygous deletions and duplications can play an important role in the pathogenesis of PD and can be considered as dominant mutations with low penetrance.