Molecular chaperones, or heat shock proteins (HSPs), constitute a highly conserved class of proteins responsible for the correct folding of polypeptides and the prevention of their misfolding and aggregation, thereby maintaining cellular proteostasis. These proteins are classified into several families based on molecular weight — including HSP40, HSP60, HSP70, HSP90, HSP110, and small HSPs — and act in coordination with co-chaperones as central components of the cellular protein quality control system. Chaperones participate in numerous cellular processes, including the folding of newly synthesized proteins, refolding of denatured or unstable proteins, assembly of protein complexes, disaggregation, and degradation of defective polypeptides.
Through these mechanisms, HSPs protect cells from stress (e.g., heat shock) and support protein homeostasis; activation of the chaperone response is regulated by heat shock transcription factors (HSFs) in response to stress stimuli.
Dysfunction or imbalance in chaperone activity is associated with a range of pathologies: in neurodegenerative diseases, the accumulation of toxic protein aggregates (such as amyloid-beta and tau in Alzheimer’s disease) is counteracted by HSP activity, whereas in cancer, the overexpression of HSPs contributes to tumor cell survival and malignant progression. Given their pivotal role, molecular chaperones are actively investigated as targets for therapeutic modulation. Pharmacological inhibitors of HSP90 are currently undergoing clinical trials as anticancer agents, while HSF1/chaperone inducers and gene therapy strategies are being explored to enhance proteostasis in proteinopathies. Promising directions also include vaccines based on HSP–antigen complexes, which utilize chaperones as adjuvants to stimulate immune responses, as well as proteostasis-oriented therapies aimed at restoring protein homeostasis within the cell.

Elective single embryo transfer (eSET) is a cornerstone of modern reproductive medicine, aimed at achieving a healthy singleton birth while minimizing the risks associated with multiple pregnancies. Enhancing its efficacy requires the refinement of embryo selection methods, among which preimplantation genetic testing for aneuploidy (PGT-A) holds significant importance. The widespread adoption of PGT-A, particularly through next-generation sequencing (NGS), has led to an increased detection of mosaic embryos, which contain a mixture of euploid and aneuploid cells.
This literature review examines the biological underpinnings of embryo mosaicism, whose primary cause is mitotic errors during early embryogenesis. The challenges of laboratory diagnosis and the interpretation of PGT-A results are analyzed in detail, focusing on technical limitations, variability in diagnostic thresholds, and the discordance in chromosomal status between the trophectoderm and the inner cell mass.
Data from clinical studies on the outcomes of mosaic embryo transfers are presented. The evidence indicates that pregnancy and live birth rates following the transfer of embryos with low– and intermediate-level mosaicism can be comparable to those achieved with euploid embryos.
The positions of international professional societies (ESHRE, ASRM, PGDIS) are reviewed. These bodies concur that mosaic embryos should not be considered a priori unsuitable for transfer. The decision to transfer such embryos must be deliberate, involving a genetic counselor or clinical geneticist, and tailored to the individual patient’s circumstances. While the transfer of euploid embryos remains the priority, mosaic embryos represent a viable alternative when no euploid embryos are available, with prenatal diagnostic testing being strongly recommended in these cases.

Disorders of somatic mosaicism represent a heterogeneous group of conditions caused by postzygotic variants in genes regulating cell growth, proliferation, and angiogenesis. Their phenotypic manifestations are highly variable and often overlapping, making molecular genetic testing essential for accurate diagnosis and therapeutic decision-making. In this study, we applied a custom NGS panel targeting genes involved in overgrowth syndromes and vascular malformations to a cohort of patients with suspected PROS and other mosaic disorders. Pathogenic or likely pathogenic variants were detected in 65,8% of cases, indicating a high diagnostic efficiency of the developed panel. The variant allele frequency was generally below 20%, highlighting the need for high-depth sequencing to detect lowlevel mosaicism. The study also demonstrated the utility of this approach for differential diagnosis of mosaic overgrowth and vascular disorders beyond PROS. Thus, high-depth targeted NGS of the developed panel proved to be an effective tool for precision diagnostics, selection of targeted therapy, and expanding the genetic spectrum of mosaic disorders.

Objective. To determine the spectrum and relative frequencies of pathogenic variants of the ATP7B gene and to study the relationships between the genotype and phenotype of the disease in Russian children with Wilson-Konovalov disease.
Methods. The study included 100 children (3-17 years old) with a genetically verified diagnosis of fibroid tumor, observed in the period 2012-2023, who underwent a comprehensive examination: the level of ceruloplasmin in the blood and daily excretion of copper in the urine were determined, magnetic resonance imaging of the brain, ophthalmological examination using a slit lamp, indirect fibroelastometry (the degree of fibrosis was assessed using the METAVIR scale). A search for specific variants of the ATP7B gene was performed using real-time PCR, Sanger sequencing, and high-throughput sequencing (HTS).
Results. 51 pathogenic variants of ATP7B were detected, including 14 previously unknown. The most common variants were c.3207C>A, detected on 45.5% of alleles, c.3402del – 6.5%, c.3190G>A – 6%, and c.2304insC – 5.5%. The presence of the major c.3207C>A genotype is associated with late onset and mild liver damage, while the presence of variants leading to premature translation termination are associated with early onset, severe liver damage, and lower ceruloplasmin levels (p < 0.001). The diagnostic efficacy of the standard PCR panel, assessed by the detection of two pathogenic variants, was only 39%, while the high-throughput sequencing allowed the identification of biallelic variants in 99% of patients.
Conclusion. A unique spectrum of ATP7B gene variants with pronounced genetic heterogeneity has been identified in the Russian children with WKD. The established relationships between WKD genotype and age of onset, the degree of liver damage, and ceruloplasmin levels offer potential for predicting the course of the disease and improving diagnostic algorithms.

This study is the first to investigate the association of GWAS polymorphisms with the risk of multiple uterine fibroids (UFs). Genotyping of 17 SNPs was performed in 570 patients with UFs (337 with multiple and 233 with single nodules) using real-time PCR. The T allele of the rs2235529 variant in the WNT4 gene was significantly associated with an increased risk of multiple UFs (OR = 1.51; 95% CI = 1,04–2,18; p = 0.026). Functional interpretation indicated that this allele influences the binding sites for transcription factors involved in key pathways of proliferation, inflammation and muscle organ development, and is also associated with an increased BMI. These results suggest that the rs2235529 variant in WNT4 could serve as a potential biomarker for the personalized prediction of multiple UF risk.

Determination of 7TA – repeats in the promoter of the UGT1A1 gene (rs3064744) can’t always explain the presence of clinical symptoms in patients with Gilbert’s syndrome (GS) phenotype. During sequencing of the exons and part of promoter of the UGT1A1 gene in 24 individuals with the GS phenotype, a single nucleotide variant rs28899472 of the UGT1A1 gene of uncertain clinical significance was found in a heterozygous state in 3 individuals. The aim of the study is to search for an association between GS and the rs28899472 variant of the UGT1A1 gene. We found that the CT genotype of the rs28899472 variant of the UGT1A1 gene is a risk genotype for the GS phenotype, while the CC genotype is protective in its relation. An association between the CT genotype and the level of total and unconjugated bilirubin was established.

Pathogenic variants in the WFS1 gene play a key role in the etiology of Wolfram syndrome, a rare hereditary disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and various additional clinical manifestations of highly variable severity. The study included 518 individuals: 318 unrelated patients with a monogenic diabetes phenotype and 200 biological relatives of the patients. Using next-generation sequencing, we identified rare WFS1 gene variants (c.1943G>A (p.Trp648*), c.2225G>A (p.Cys742Tyr), c.1124G>A (p.Arg375His) и c.1336A>C (p.Ser446Arg)). The clinical presentation among patients ranged from isolated diabetes mellitus to a combination of endocrine, sensory, and neurological impairments in carriers of the same variant. These findings highlight marked phenotypic heterogeneity and underscore the necessity of a comprehensive diagnostic approach to monogenic diabetes, incorporating thorough clinical evaluation and careful interpretation of genetic testing results.

Background. Single nucleotide polymorphisms (SNPs) rs9982601 (KCNE2), rs17087335 (NOA1), and rs2048327 (SLC22A3) have been associated with the risk of coronary artery disease (CAD) in genome-wide association studies (GWAS), but have not previously been studied for their impact on the efficacy of rosuvastatin therapy.
Aim: to establish the association of these SNPs with the effectiveness of lipid-lowering rosuvastatin therapy and to validate their association with the risk of CAD in the population of Central Russia.
Methods. 1960 individuals were included in CAD risk study; 116 patients with CAD were included in the pharmacogenetic study. The change in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) was studied during 1, 6, and 12 months of rosuvastatin therapy. SNP genotyping was performed using the MassARRAY 4 genomic mass spectrometer and real-time polymerase chain reaction. The association of SNPs with the risk of CAD and with change in lipid levels was analyzed using logistic and linear regression, respectively, in PLINK v1.9 software.
Results. SNP rs9982601 was associated with the enhanced lipid-lowering effect of rosuvastatin in terms of TC reduction (p = 0,046). The association of above SNP with CAD risk was validated (OR 4,23 95% CI = 1,91-9,40; p<0,001). Rs17087335 and rs2048327 SNPs were associated neither with rosuvastatin efficacy nor CAD risk.
Conclusion. For the first time, the influence of GWAS-associated locus for CAD rs9982601 (KCNE2) on the lipid-lowering effect of rosuvastatin was established, and its association with the risk of CAD in residents of Central Russia was validated.

A change in microRNA expression, which can be influenced by a change in the methylation level of microRNA gene (MIR) promoters, is observed as a biochemical marker of carotid atherosclerotic plaques (ASP) instability. The aim of our work was to identify microRNAs with the strongest correlation between the level of methylation of CpG sites in the promoter region of MIR genes and the expression of mature microRNAs in atherosclerotic plaques of human carotid arteries. DNA and microRNA for analysis were isolated from the ASP of patients with advanced carotid atherosclerosis (n=14). DNA methylation was analyzed by the methyloarrays, and microRNA expression was analyzed using the microRNA–seq. The expression of miR-23b-3p and miR-27b-3p was inversely correlated with the methylation of cg09951047, cg20355301 and cg13972491. The results obtained indicate the important role of methylation of the MIR23B gene promoter in regulating the expression of the miR-23b/-27b/ -24-1 cluster in atherosclerotic lesions of the carotid arteries.

The development and control of inflammation are governed by intracellular signaling pathways that form a multicomponent network regulatory structure. The efficiency of interaction between individual elements of this network can be modified by various factors, including genetic polymorphism. This article discusses the results of a study conducted in a sample of the Russian population of the Siberian region (n = 192), focusing on the spectrum and frequencies of polymorphic variants of the VDR and NFKB1 genes and their functional partners — 33 polymorphic variants across 11 genes. The study identified 283 complexes of polymorphic variants in the «vitamin D – VDR» system genes (including 4 with a frequency >1%) and 154 complexes in the «NF-kB1 – 20S proteasome» system genes (20 with a frequency >1%).