Plasma cell neoplasms are a multifocal neoplastic proliferation of plasma cells that secrete a monoclonal protein. During the formation of multiple myeloma, a multistep process of cell transformation occurs, including changes in the genetic profile due to additional events such as somatic mutations, epigenetic and chromosomal changes, which leads to the progression of the disease from monoclonal gammopathy of unspecified significance to symptomatic multiple myeloma and, ultimately, in some patients to aggressive extramedullary disease. The profile of genetic changes associated with the progression of plasma cell neoplasms includes single nucleotide polymorphisms in the genes of the MAPK signaling pathway. Proteins of the RAS and RAF families are components of the RAS/RAF/MEK/ERK signaling pathway, which transmits external signals into the cell nucleus. Single-nucleotide polymorphisms in the RAS and RAF genes lead to aberrant activation of the MAPK signaling pathway cascade reactions, causing changes in the cell cycle and mediating malignant transformation of cells.

Preeclampsia (PE) is a severe medical condition affecting pregnant women, often developing after 20 weeks, and is the most common serious disorder during pregnancy, contributing to 2%-8% of pregnancy-related complications worldwide. The goal of this study is to investigate the association of two genetic variants in NOS3 (-786T>C; rs2070744) and (894G>T; rs1799983) with the risk of developing PE in Russian pregnant women from Rostov region. The case–control study involved 106 pregnant women (46 pregnant women with PE and 60 healthy controls). Genotyping of the selected NOS3 genetic variants (-786T>C) and (894G>T) was done using allele specific RT-PCR. Multifactor dimensionality reduction (MDR) was used to assess the relationship between the SNP-SNP interaction and risk of developing PE. In addition, we analyzed the linkage disequilibrium (LD), and haplotypes association for the selected SNPs in the studied population. According to our results, both NOS3 polymorphisms were statistically significant (P=0.004 and P=0.045, respectively). The NOS3 -786(TT) genotype (OR=0.25 95% CI [0.11- 0.58]) and the NOS3 894(GG) genotype (OR=0.38 95% CI [0.17- 0.84]) were associated with low risk of developing PE. While -786(TC) genotype (OR=4.17 95% CI [1.76-9.85]), 894(GT) (OR=2.48 95% CI [1.10-5.63]) and dominant model of NOS3 (-786T>C) TC+CC (OR=3.97 95% CI [1.72-9.14]) as well as the dominant model GT+TT of NOS3 (894G>T) (OR=2.64 95% CI [1.20-5.82]) were associated with increased risk of PE. In addition, the polymorphism -786(C) allele (OR=2.21 95% CI [1.23-3.98]) and polymorphism 894(T) allele (OR=2.14 95% CI [1.15-4.01]) were both associated with an increased risk of PE. According to the MDR results, the SNP-SNP interaction was statistically significant (P=0.0003). Moreover, two haplotypes of NOS3 gene variants -786C*894G (OR=3.01 95% CI [1.15- 7.86]; P=0.027) and -786C*894T (OR=3.03 95% CI [1.27-7.23]; P=0.014) were shown to be statistically related with an elevated risk of PE. 

Myocardial infarction (MI), being the main complication of coronary heart disease (CHD), is one of the most common causes of death and disability in the adult population. Currently, there is an increase in the incidence of MI at a young age. An independent risk factor for MI at a young age is hereditary predisposition. In this work, we searched for rare genetic variants associated with the development of cardiovascular diseases using whole-exome sequencing in patients who had suffered an MI before the age of 45 years, and for whom the main genetic risk factors for MI − monogenic dyslipidemias and thrombophilia – were excluded. In two patients, rare variants of the SYNPO2L gene were identified − p.(Arg630Leu) (rs143723429) and a previously undescribed variant p.(Arg910Gln), leading to amino acid substitutions that can lead to dysfunction of the corresponding protein. The data obtained suggest the involvement of the SYNPO2L gene, encoding a protein of contractile muscle function, in the pathogenesis of early MI.

Mitochondrial myopathy caused by thymidine kinase 2 (TK2) deficiency is an inherited monogenic disease that is part of a group of mitochondrial DNA (mtDNA) maintenance and replication syndromes. These diseases mainly manifest as severe multisystem childhood forms and are characterized by a significant reduction in mtDNA copies in the affected cells and tissues. In Russia, the first cases of TK2- associated myopathy were identified in 2019. The importance of early diagnosis of the disease is due to the emergence of new treatment methods. Aim of the study: to conduct selective screening for TK2 deficiency among 150 patients with a previously excluded diagnosis of spinal muscular atrophy, as well as 50 patients with a presumptive diagnosis of congenital myopathy with a negative test result using panel sequencing. Method: high-throughput sequencing using a panel of mitochondrial disease genes. Results: One heterozygous carrier of a pathogenic variant in the TK2 gene was identified. Additional analysis of Russian exome sequencing databases Ruexac, Ru-seq browser showed an estimated frequency of TK2 deficiency equal to 1:563900, confidence intervals CI (95%) – 218,894:1,454,451. 

Background. Along with common risk factors for cardiovascular disease (male gender, hypertension, smoking) the predisposition to the development of ascending aortic aneurysm is also largely determined by genetic factors. The genetic variants underlying the development of ascending aortic aneurysm are localized in the genes of connective tissue components, smooth muscle cell function, and the TGF-β signaling pathway. However, to date, a panel of genetic markers recommended for assessing the risk of developing sporadic cases of ascending aortic aneurysm has not yet been fully developed.Aim: to determine clinically significant genetic variants in a patient with a sporadic ascending aortic aneurysm using the massively parallel sequencing.Methods. We searched for rare genetic variants (minor allele frequency <1%) localized in exons of 53 genes of hereditary and syndromic forms of ascending aortic aneurysm in peripheral blood DNA of a patient (48 years old, diameter of the ascending aorta 50 mm). Clinical exome sequencing was performed on the SOPHiA GENETICS platform. Variant annotation was performed using the ANNOVAR program. Classification of variants according to the degree of pathogenicity was carried out according to the standards and recommendations of the American College of Medical Genetics (ACMG) using the VarSome tool with further validation of identified variants by Sanger sequencing.

Results. The sequencing revealed three variants of uncertain significance (VUS) in the following genes: FBN1 c.C7841T (p.A2614V), COL3A1 c.A2498T (p.K833I), and PLOD3 c.G833A (rs1041461490, p.G278D). Detected variants were not previously reported in relation with ascending aortic aneurysm. Two variants are localized in genes with a proven maximum effect of mutations on the development of ascending aortic aneurysm (FBN1, COL3A1). The third gene, PLOD3, is associated with diseases of the ascending aorta based on experimental studies, but in clinical practice its role in the development of ascending aortic aneurysm has not yet been established. Conclusion. Sporadic ascending aortic aneurysms have the same underlying pathogenic pathways as hereditary and syndromic forms. However, the combination of genetic variants found in sporadic cases is unique. To identify these distinctive features in patients with sporadic ascending aortic aneurysm genetic testing using an advanced panel is required. The development of extended genetic panel is a challenge for specialists in cardiogenetics.

The brief report presents the results of the analysis of genetic diversity and the structure of linkage disequilibrium in two populations of southern Altaians: Telengites and Altai-Kizhi. The analysis was performed using the TYPER X-19 multiplex set, which includes 18 STR markers localized on the X chromosome. The specificity of the genetic structure of the two ethnic groups is demonstrated, and differences in the structure of linkage disequilibrium are revealed. The assessment of the level of identification informativeness of 18 X-STR for DNA identification was carried out.

The article summarizes the results of the description of the population and genetic characteristics of the population of North Ossetia - Alania, obtained during a comprehensive genetic and epidemiological survey of the population of the Republic. The correlation analysis showed a good correspondence of the obtained parameters.