Hereditary tyrosinemia type I is a hereditary disease of the tyrosine amino acid metabolism. Two clinical variants are distinguished: acute (type 1A) and chronic (type 1B). The acute form is characterized by early onset, severe hepatic failure and intoxication, while the chronic form manifests itself at an older age and is less offensive in the debut. The prognosis is not dependent on the form of the disease: all the patients with tyrosinemia type I eventually get liver cirrhosis and are at high risk of developing hepatocellular carcinoma (HCC) or hepatoblastoma. Pathogenetic therapy of the disease with Nitisinone and tyrosine-free diet have been developed. Treatment is most effective when administered at an early stage, therefore tyrosinemia type I is included in the neonatal screening program in Russian Federation. Our work presents three clinical cases of late diagnosis of tyrosinemia type I with the development of liver fibrosis, hypophosphatemic rickets and blood coagulation disorders. It was demonstrated that even late initiation of pathogenetic therapy, despite the reduced efficiency, significantly improves the patient’s quality of life. Although neonatal screening for HT1 has been introduced, exclusion of this disease is still necessary in children and adolescents with early manifestation of liver pathology.

Introduction. Neural tube defects (NTDs), being frequent and severe developmental defects, remain a significant cause of mortality and morbidity in newborns, and make a significant contribution to the structure of stillbirth causes. To plan the volumes and implement preventive measures aimed at reducing the level of NTDs, it is important to know the epidemiological characteristics of defects in the regions of the Russian Federation.

Aim: to estimate the frequency of neural tube defects in the regions of the Russian Federation based on monitoring of congenital defects.

Methods. The study included a retrospective analysis of the database of epidemiological monitoring of congenital malformations (CM), covering a 13-year period (2011-2023). The material was data from 33 regions of the Russian Federation that regularly monitor CM. The study included cases of defects among live births, stillbirths, as well as eliminated fetuses with NTDs.

Results. During the analyzed period, 7989 cases of NTDs were registered in the congenital malformations monitoring database, the total number of newborns was 6,834,020. The total incidence of NTDs was 11.69 per 10,000 births (95% CI 11.56-11.82). Among all cases of NTDs, live births accounted for 22.32%, stillbirths – 4.03%, and eliminated fetuses – 73.65%. Regional frequencies ranged from 3.25 to 19.99 per 10,000 births. In the NTD group, the most common defect is spinal bifida, while encephalocele is a rare defect. During the study period, the level of NTDs in all regions remains stable, however, in recent years (2020-2023) there has been a slight decrease in the level of NTDs, which is due to secondary prevention measures.

Conclusions. NTDs remain common congenital malformations. During the analyzed period, the frequency of this group of defects remains stable. The observed decrease in the level of NTDs among newborns is the result of second-level preventive measures. Obviously, in order to reduce the overall incidence of NTDs, it is necessary to increase the effectiveness of primary prevention (raising awareness of women of reproductive age about the possibilities of reducing risks, timely intake of folic acid).

Angiogenesis plays an important role in the metabolism of cardiomycotes, affecting their functioning and vital activity, as well as the process of cellular aging. The aim of the study was to determine the expression level of angiogenesis inhibitor genes in the heart of Wistar rats under low-dose exposure to doxorubicin. The study included two groups of 10 male Wistar rats, the expression of angiogenesis genes was determined using qPCR. The experimental group was characterized by increased expression of the Il1rn and Rnh1 genes. Low-dose subacute exposure to doxorubicin indirectly activates the expression of angiogenesis inhibitor genes, which aggravates the cardiotoxic effects of the toxin.

Endocrine ophthalmopathy is an extrathyroidal lesion of Graves’ disease, the pathogenesis of which is not fully understood. The clinical picture of this lesion is polyvariant, which creates difficulties in determining individual treatment; there are no clear criteria for assessing the effectiveness of the therapy. The causes of glucocorticoid resistance in patients with endocrine ophthalmopathy remain controversial to this day. The development of epigenetics has brought a lot of new information both to the understanding of the development of the pathogenesis of this disease, the formation of its clinical forms, and to the understanding of the causes of a negative response to glucocorticoid therapy, which has remained the gold standard in treatment for 67 years. MicroRNAs, which have attracted the attention of researchers in the last two decades, are necessary for the normal development of various physiological systems of the body; changes in their expression are associated with the development of many human diseases, including autoimmune diseases, which include endocrine ophthalmopathy.

Overgrowth and vascular malformations syndromes are associated with somatic variants arising during embryogenesis in cell proliferation and angiogenesis genes. The broad phenotypic heterogeneity of these syndromes complicates clinical diagnosis, making molecular genetic testing crucial for establishing a definitive diagnosis. In this study, deep NGS sequencing of a targeted panel of genes associated with overgrowth syndromes and vascular malformations was performed in 160 patients. Pathogenic and likely pathogenic variants were identified in 91 patients (57%), with 53 PIK3CA variants (58%).

The clinical characteristics were assessed and a genetic cause was sought in 126 patients (55 girls and 71 boys) with obesity (SDS BMI>3.0) at an early age (up to 7 years). The median age of patients at the time of examination was 9.2 years. Nucleotide sequence changes in 37 genes were detected in 49.7% of children. In patients with obesity of unknown cause, a burdened hereditary history of obesity was statistically significantly more common than in patients with genetic disorders (p<0.001). 

The relationship of the polymorphic genes AGT (rs699), eNOS (rs2070744), AGTR1 (rs5186), and AGT (rs4762) and cardiovascular risk in workers in the mechanical engineering industry was analyzed. It has been shown that in women exposed to harmful occupational factors such as noise, vibration and severity of labour in excess of hygienic standards, the A/C genotype of the rs5186 polymorphic variant demonstrates a protective effect on the risk of developing hypertension (OR = 0.09, 95% CI: 0.01 – 0.77 and OR = 0.08, 95% CI: 0.01 – 0.71, respectively). In men, the C/T polymorphic variant rs2070744 genotype increases the risk of hypertension when working in excessive noise and vibration (OR =6.21, 95%CI: (1.06-36.40), and in severity of labour (OR =6.14, 95%CI: (1.04-36.39).

There are two challenges that need to be addressed today in the genotoxicity testing. The first one includes improvement of in vitro testing methodology and development of high-throughput test systems for genotoxicity screening. The second one is determined by the necessity to develop new methods to register gene mutations in vivo, including genotoxicity in germ cells. Current methodological achievements promising for solving the above tasks are considered.

Alport Syndrome (AS) is a heterogeneous progressive disease characterized by nephritic syndrome, often sensorineural deafness, and less frequently ophthalmological symptoms. There are autosomal dominant, autosomal recessive, and X-linked AS. he prevalence of Alport syndrome averages 1:5,000-10,000 newborns. The disease is caused by pathogenic and likely pathogenic variants in genes encoding α3, α4, and α5 chains of type IV collagen (COL4A3, COL4A4, COL4A5). Pathological variants in these genes account for 20-30% of chronic kidney diseases and end-stage renal disease in adulthood among inherited nephropathies. There were examined 327 unrelated patients, for 130 of whom the diagnosis was confirmed. X-linked inheritance was identified in 47%, autosomal recessive in 6.9% of cases, and autosomal dominant in 39.2%, what differs from the distribution structure of AS forms in the world. Repeating variants matching the literature data have been identified in all three genes. There was no clear correlation between the more severe course and the type of mutation in any of the genes.

Usher syndrome (USH) is a rare genetic disorder characterized by a combination of sensorineural hearing loss, retinitis pigmentosa, and, in some cases, vestibular disorders. It is inherited mainly by autosomal recessive type. Also, there are forms with digenic types of inheritance. The incidence of the disease in the world varies from 3 to 6.2 per 100,000 people. Currently, there are 4 clinical types of USH associated with 16 genes. The genes encode proteins involved in the formation and maintenance of the functions of stereocilia of inner ear hair cells and retinal receptors.

Data from patients with genetically confirmed USH were used to analyze the results. The total sample is 69 individuals from 63 families. Routine clinical and high-tech instrumental, molecular-genetic methods were applied, and medical and genetic counseling was carried out.

Neurosensory hearing loss was detected in all patients, but the earliest and most severe form is found in type 1 USH. Vestibular disorders are most common in type 1. Clouding of the lens and the presence of cystic macular edema are characteristic of type 2 USH. Retinitis pigmentosa was found in all patients in the sample. However, there was an atypical form of PR with central retinal zone lesion.

Molecular genetic diagnostics performed by high-throughput sequencing of the target gene panel and/or complete exome and/or genome, multiplex ligase-dependent amplification (MLPA), Sanger family segregation analysis allowed to determine the most frequent types of USH – type 1 and type 2 (52% and 42%, respectively). In type 1, the most frequent were pathogenic variants in MYO7A gene, in type 2 – in USH2A. Type 3 USH is the least frequent type (6%). The results obtained necessitate further study of this problem.

Obesity is a serious social and medical problem. The study is conducted on the basis of the population sample of the HAPIEE project. Groups of women were formed, selected by body mass index (BMI) using WHO criteria. Approximately 100 people in each group, starting from 18.5-25 kg/m². Age 45-69 years (n=520). 11 nucleotide sequence variants (NSVs) were genotyped: rs9939609 FTO, rs17782313 MOC4R, rs3810291 ZC3H4, rs7903146 TCF7L2, rs1799883 FABP2, rs1800497 DRD2, rs12940622 RPTOR, rs1800437 GIPR, rs1561589 CTBP2, rs6773957 ADIPOQ, rs13021737 chr. 2. Genotype frequencies were analyzed in groups with different BMI, body roundness index (BRI), morbid obesity (MO), and abdominal obesity (AO). Significant differences were obtained in the groups of women divided by BMI by genotype frequencies: rs9939609, rs17782313, rs3810291, rs12940622, rs1800437, rs7903146. Significant associations with the body roundness index were obtained: rs9939609, rs17782313, rs3810291, rs12940622, rs7903146. rs9939609, rs12940622 were associated with abdominal obesity. Associated with morbid obesity: rs9939609, rs12940622, rs1561589. Conclusion. rs9939609, rs17782313, rs3810291, rs12940622, rs1800437, rs13021737, rs1561589, rs7903146 are associated with different obesity phenotypes in women in the urban Caucasian population.

The low availability of some types of molecular genetic diagnostics often forces doctors and patients to make a difficult choice between different research methods, but in some cases only the combined use of molecular and classical cytogenetics methods or different types of molecular methods can provide complete information about the cause of genetic pathology and further risks in a particular family. The article provides several examples of how the integrated use of different cytogenetic diagnostic methods allows for a correct diagnosis, a prognosis for the patient, and reproductive tactics for the family.

Rapid methods of testing two major mutations Cys139Gly and G219del in familial hypercholesterolemia (FH) in St. Petersburg using restriction and heteroduplex analysis are proposed.

The goal is to identify personality factors associated with a polymorphic marker of susceptibility to Alzheimer’s disease. The relationship between quantitative character traits determined using Cattell’s psychodiagnostic method (16 factor personality questionnaire, 16PF) and the polymorphic variant rs1466662 in the DCHS2 gene was analyzed. DNA samples from 172 students were genotyped by MALDI-TOF mass spectrometry. The obtained data were processed by the nonparametric Kruskal-Wallis test. Non-random associations were established with factor A (withdrawal – sociability) in the general sample of medical university students under a codominant type of inheritance (р = 0.018). A connection was found between this variant and factor F (restraint – expressiveness) for an autosomal recessive type of inheritance (р = 0.016) in males, and factor F4 (conformity – independence) under an overdominant type of inheritance (р = 0.031) in females. The findings likely indicate a partially overlapping genetic component of susceptibility to Alzheimer’s disease and variability in personality traits.

Introduction. Not always patients with cystic fibrosis (CF) have clinical manifestations characteristic of the disease, which is determined by the patient’s genotype. The «ICM» method plays a special role in diagnostics with borderline sweat test values and rare genetic variants.

Objective: to evaluate the use of the intestinal current measurement (ICM) method for clinical practice.

Methods. ICM was carried out according to the European SOP V2.7_26.10.11. 154 people were examined: 18 healthy people (control group), 36 patients with suspected cystic fibrosis, 100 patients with cystic fibrosis (genetic variants of various classes – I, II, IV, V) of which 21 patients with rare genetic variants not described earlier, the effectiveness of targeted therapy was assessed in 34 patients.

Results. 36 patients with suspected CF (carriers of 1 CFTR variant, atypical clinical picture) were examined. The diagnosis was removed in 23 patients, and confirmed in 10. The following genetic variants were identified and described for the first time: 1898+2T>C, G1047S, 3321delG, 712-1G>T, Q1352P, c.1584+18672A>G, E873X, D443fs, W277X, W361X, D579Y, N505H, E403D, S1455X. The function of ion channels was studied in the variants typical for the Russian Federation: E92K, W1282R, N1303K, R334W, 3272-16T>A, in carriers of complex alleles F508del;L467F, S466X;R1070Q and E217G;G509D. The effectiveness of targeted therapy was assessed in 34 patients.

Conclusions. The ICM method helps clinical physicians establish or exclude the diagnosis of cystic fibrosis, especially in the case of newly identified genetic variants of the CFTR gene, and assess the effectiveness of therapy with CFTR modulators.

It is known that increased concentration of coal dust in the air of the working area of enterprises leads not only to the development of inflammatory diseases of the respiratory system, but also to increased genomic instability in the cells of the immune system, which can have extremely unfavorable consequences. Miners of coal mines of Kuzbass (n = 507), employees of coal thermal power plants (n = 455) and residents of the same area not engaged in industrial production (n = 798) were examined. The frequency of structural chromosomal aberrations (CA) was assessed, a micronucleus (MN) test was performed on blood lymphocytes with a cytochalasin block, the frequency of hypermethylation of promoters of key repair genes (XRCC1, XRCC2, XRCC3, XRCC4, ERCC2, ERCC5) was studied using methyl-specific polymerase chain reaction. It was found that all workers had an increased frequency of CA, MN, bridges, protrusions. An increase in the frequency of occurrence of hypermethylated and methylated statuses of promoters of the studied genes was noted.

To date, more than 30 genes have been identified as causes of monogenic diabetes, including neonatal diabetes mellitus and MODY. Understanding the molecular pathogenesis of inherited forms of diabetes mellitus helps expand the boundaries for future research aimed at improving diagnostic accuracy and developing personalized therapeutic strategies. As part of this work, a NGS panel was developed to search for mutations in 28 genes associated with the development of hereditary diabetes mellitus in 506 unrelated patients from various regions of the Russian Federation. The study identified 180 pathogenic or likely pathogenic variants in 13 target genes (GCK, HNF1A, HNF1B, HNF4A, ABCC8, INS, INSR, KCNJ11, PAX4, PDX1, ZFP57, BLK, WFS1), which is 46,44% of the analyzed sample (235 people).

Background. Social functioning is an important aspect of schizophrenia, affecting patient’s quality of life and prognosis. Genetic factors, including OXTR and AGER gene polymorphisms, potentially participate in the regulation of social behavior by interacting with adverse childhood experiences (ACEs).

Aim: to evaluate the contribution of OXTR rs1042778 and AGER rs1800625 polymorphisms to the development of social disadaptation in patients with schizophrenia, with the effect of AСEs taken into account.

Methods. A sample of 507 patients with schizophrenia were included in the study. Social functioning was assessed using the PSP scale, clinical symptoms were assessed using the PANSS. OXTR rs1042778 was genotyped using HRM method, AGER rs1800625 determined based on genome-wide genotyping data. Statistical analysis was performed using ANCOVA, adjusting for gender and disease duration.

Results. The association of AGER rs1800625 polymorphism with more prominent social deficit in the area of disturbing and aggressive behavior was revealed. A combined effect of OXTR rs1042778 and AGER rs1800625 polymorphisms was observed in relation to the level of prosocial behavior.

Conclusion. The results obtained confirm the role of AGER rs1800625 and OXTR rs1042778 in the regulation of social functioning in schizophrenia, opening prospects for further study of the interaction of genetic and environmental factors.

Gene therapy by local delivery of target genes using gene-activated matrices (GAM) for the treatment of patients with bone diseases represents a promising approach. The aim of the work is a comparative study of the osteoinductive effect of GAM based on adenoviral or plasmid vectors with the BMP2 gene in vitro and in vivo. Using RT-PCR, ELISA, alizarin red staining and micro-CT, it was shown that the developed GAM provide delivery of the target gene to cells, stimulate osteogenic differentiation and reparative neoosteogenesis during intraosseous implantation.

Clinical and laboratory diagnosis of hereditary metabolic diseases is difficult. In the group of patients with DNA-verified diagnosis, a high prevalence of immunological, neurological and nephrological disorders in pediatric patients was noted. Increased awareness among health care workers and the availability of metabolic tests can facilitate early diagnosis. NGS methods show high diagnostic value.

Autosomal recessive forms (AR-IRD) account for the largest proportion of cases of inherited retinal diseases (more than 50% of all detected pathology). However, due to the high prevalence of pathogenic recessive variants in the general population, it is difficult to establish whether the variant is the cause of the disease or reflects an incidental carriage. Therefore, the aim of the present study was to evaluate the prospects of finding a second variant in frequent AR-IRD genes (ABCA4, CNGB3, USH2A, CRB1, RPE65, CEP290 and EYS) based on population data and to identify «elusive» variants on the second allele by routine methods using whole genome sequencing (WGS). WGS data were retrospectively analyzed for 106 patients. Of these, 45 (42.5%) were able to establish a molecular diagnosis, of whom 27 (60%) carried a variant in the target gene on the second allele. In the remaining 18 patients mutations in other genes with different types of inheritance were detected. The most common genes in which CNVs and intronic variants were more frequently reported were the EYS, USH2A, and ABCA4. WGS increased the percentage of solved cases of IRD by 3%, but this figure would be significantly higher if all patients with an unconfirmed molecular diagnosis were included in the study.

Uterine fibroids (UF) and benign ovarian tumors (BOTs) are characterized by common risk factors that affect the level of sex hormones; however, the common genetic component of these diseases is poorly understood.

The aim of the study was to investigate the association of GWAS-significant UF loci with the risk of BOTs development against the background of UF.

Materials: genotyping of 654 DNA samples of UF patients (including 59 with comorbid BOTs) was performed by real-time PCR.

Results: SNP rs66998222 LOC102723323 G/A is associated with a reduced risk of BOTs (OR = 0.47, 95% CI = 0.27-0.85, p = 0.006).

Conclusions: Bioinformatics analysis showed that SNP rs66998222 LOC102723323 may be associated with the risk of BOTs through involvement in the regulation of cytokine pathways, inflammation, obesity, and age at menarche.

Introduction. Сurrently, the task of modern medicine is to study the relationship between the clinical picture of patients and the data of a molecular genetic examination.

Aim. Analysis of the phenotypic diversity of Kabuki type 1 syndrome depending on the genetic variant. The study included 21 patients with Kabuki syndrome type 1.

Results. Depending on the type of genetic variant, patients were divided into 3 groups: group 1 –nonsense variants (n = 13 (61.9%)), group 2 – variants leading to a shift in the reading frame (n = 6 (28.6%)), group 3 – variants of the splicing site (n = 2 (9.5%)). As a result of the analysis of patients with Kabuki syndrome type 1 it was found that immunodeficiency is significantly more common among patients in the group of free-shift variants compared to children from the group of nonsense variants. For the first time it was discovered that nephrocalcinosis is diagnosed in a high number of patients (33.3%). The study revealed a patient with Kabuki syndrome, type 1 and infantile hypercalcemia, type 1, which poses significant obstacles for the prognosis of the development of severe nephrological complications.

Aim: analysis of the frequency of mutations in GNAQ/GNA11 genes in circulating tumour DNA and genotypes of polymorphic marker C3435T of ABCB1 gene.

Methods. Between 2015 and 2022, 272 patients with intraocular melanocytic neoplasms were examined. Patients were divided into study groups (choroidal melanomas, group I (n=141), suspicious, group II (n=67) and beingn, group III (n=64) choroidal nevi).

Results. In group I, at least one mutation in the GNAQ/GNA11 genes was detected in 95%, of which two mutations were detected in 24.8% and three mutations in 11.3% of patients. In group II, one mutation was detected in 73.1%, with two mutations in 4.5% of patients. In group III, one mutation in the GNAQ/GNA11 genes was detected in 13 patients (20.3%). In group II, the frequency of mutations in GNAQ/ GNA11 genes was significantly higher than in group III (OR = 10.68 (4.73 to 24.1), F=0.0000001, ξ2 = 36.64). In group I, the frequency of CC genotype of polymorphic marker C3435T of ABCB1 gene was significantly lower compared to group II, and the frequency of CT genotype was significantly higher compared to group II.

Conclusion. In the present work on 272 patients with intraocular melanocytic neoplasms a direct dependence of the frequency of mutations detection in genes on the size and character of the tumour focus was shown. The obtained results allow both screening of patients from risk groups and differentiation of patients depending on the size and nature of the tumour focus.

The problem of copy number variation (CNV) is relevant in newborn examination using high-throughput sequencing. The message addresses the issues associated with such findings. CNV were reported to 49 patients.

Central or gonadotropin-dependent precocious puberty (CPP, ICD-10: Е22.8) occurs as a result of premature reactivation of the hypothalamicpituitary-gonadal axis and the appearance of secondary sexual characteristics in children under 8 years of age in girls and under 9 years of age in boys. The aim of this study is to determine the impact of genetic and epigenetic factors underlying the clinical phenotype of CPP. It was shown that CPP may be the result of the clinically significant genetic variants in the imprinted genes DLK1 and MKRN3 with a combined frequency of 11.5% and epigenetic factors (epimutations in the imprinting centers of DLK1 and MKRN3) with a combined frequency of 15.4%.

Here the results of wholes transcriptome sequencing of infective endocarditis (IE) affected native heart valves are presented. Resulting to the study, the differentially expressed genes and some signaling pathways underlaying IE pathogenesis have been described.

Mutations in the CFTR gene were searched for in 632 patients with suspected CF from all over the Russian Federation. Testing was carried out in three stages: search for common mutations, sequencing, and search for large deletions/duplications in the CFTR gene. The molecular genetic cause of the disease was identified in 372 (58.8%) probands. In 243 of them was at the first stage of testing. The high efficiency of the common mutation screening system is further supported by the fact that in 357 (96%) patients, at least one variant was detected using the common mutation screening system. However, sequencing and searching for large rearrangements revealed pathogenic variants that occur with a higher frequency than the variants in the common mutation screening system, which indicates the need to expand this system. Clarifying and expanding the spectrum of genetic variants leading to cystic fibrosis allows it possible to improve the diagnostic system used for first-level genetic testing in cases of suspected cystic fibrosis, thereby reducing the time and financial costs of establishing a molecular genetic diagnosis and obtaining personalized therapy.

Introduction. Miscarriage remains a significant problem in modern obstetrics, affecting 10-25% of all pregnancies. Cell adhesion molecules play a key role in the reproductive cycle, and their changes can lead to reproductive pathologies.

Aim: to study the association of the rs6131 (1057C>T, S290N) polymorphism of the SELP gene with the risk of miscarriage in the first trimester in women of the Rostov region.

Methods. The study used DNA samples obtained from the blood of 114 women (59 – control group – women with a physiological course of pregnancy, 55 – women with miscarriage (25 – with spontaneous abortion, 30 – with an undeveloped pregnancy)). DNA was isolated by thermocoagulation; nucleotide substitutions were determined by allele-specific PCR.

Results. The frequency of homozygotes for the C allele was 66.1% in the control group and 60% in the miscarriage group. The frequency distribution of genotypes and alleles according to rs6131 did not differ between the groups of women (p > 0.05).

Conclusions. The rs6131 polymorphism is not associated with a change in the risk of miscarriage in the first trimester.

LINE-1 retrotransposon is widely represented in the human genome and can function as an alternative promoter in genes. The activity of LINE-1 is regulated by DNA methylation. Previously, we showed that LINE-1 is hypomethylated in normal placenta and hypermethylated in chorionic villi of spontaneous abortions. Abnormalities in the methylation of mobile elements may affect the expression of chimeric LINE-1 transcripts. In this study, for the first time, we identified genes expressed from the alternative LINE-1 promoter in the human placenta during the first trimester of pregnancy. Chimeric transcripts of these genes are involved in placental development processes, and a deficiency in their expression could potentially lead to placental dysfunction and embryolethality.

Parkinson’s disease (PD) associated with mutations in the GBA1 gene (GBA1-PD) represents a promising target for the development of disease-modifying therapies. The GBA1 gene encodes the lysosomal enzyme glucocerebrosidase (GCase), whose dysfunction leads to the accumulation of its substrates, glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph). Previously, we demonstrated the feasibility of using primary cultures of peripheral blood macrophages as a model for identifying therapeutic targets and compounds aimed at restoring GCase activity. Transcriptomic analysis of these macrophages revealed dysregulation of the PI3K/AKT/mTOR pathway and inflammatory processes in GBA1-PD patients. In this study, we evaluated the potential of mTOR inhibitors, key regulators of autophagy, and STING inhibitors, central mediators of the immune response, as promising therapeutic strategies for reducing GCase substrate accumulation in primary peripheral blood macrophage cultures.

Using Wistar rats, as well as transcriptomics and fundamental medicine methods, the features of gene function in the brain were studied during cerebral ischemia in animals and under the influence of peptide drugs with neuroprotective properties.

A correlation analysis of polymorphic variants (SNPs) in the EPAS1 gene was conducted for 359 individuals from 52 indigenous ethnic groups of Russia and neighboring countries, taking into account their climatic and geographical characteristics. The most significant SNPs (rs17039192, rs4953342, rs6743087, rs1374749, rs4953361) were identified, and their frequency distribution was assessed across the studied populations. Specific patterns of SNP distribution among indigenous peoples of Siberia and Caucasus residents were revealed.

This study is aimed to the investigation of associations between the vitamin D metabolism genes polymorphism and inflammatory response with their soluble forms in patients with stable coronary artery disease (CAD). The obtained results indicate the association of polymorphic variants rs16944 (IL1b), rs3093077 (CRP) and rs731236 (VDR) with the CAD risk. In addition, it is noted that high levels of soluble CRP are associated with the genotypes of the rs3093077 polymorphism.

Purpose: Analysis of the frequency of molecular genetic aberrations in tumour tissue and blood in patients with iris melanoma.

Methods. 140 patients with uveal melanoma (UM) were analysed by methyl-sensitive PCR. The experimental group included 48 patients with iris melanoma (group A) and 62 patients with spread to the ciliary body (group B). Group C (comparison) consisted of 30 patients with melanoma in 2012.

Results. The spindle cell tumour type was significantly more frequent in subgroup 1p+8p (A) compared to subgroup M3+1p (A) (p=0.049), and the mixed cell type was more frequent in subgroup M3+1p (A) compared to subgroup 1p+8p (A) (p=0.049). In the subgroup of complete M3 (C), tumour spread to the ciliary body was significantly more often determined compared to other subgroups (p=0.035). In the partial M3 (C) subgroup, there was a significant association of the frequency of partial monosomy of chromosome 3 with mixed-cell and epithelioid-cell type UM (p=0.014 and 0.042, respectively). In iris melanoma, deletion of the entire short arm of chromosome 1 was found in 68.7%, chromosome 8 in 47.9%, with spread to the ciliary body in 77.4% and 51.6%, respectively, and in chorioideal melanoma in 30% and 20% of cases. No mutations in the GNAQ/GNA11 genes were detected in group A. In group B, one heterozygous mutation in GNAQ/GNA11 genes was detected in 2 patients. In group C, mutations in GNAQ/GNA11 genes were detected in 27 patients (90%). When comparing the frequency of heterozygous mutation in GNAQ/ GNA11 genes, significant differences were obtained between the experienced groups and the comparison group (F=0.0000001, χ² =56.45). The CC genotype of the C3435T polymorphic marker of the ABCB1 gene was found in 90% (F= 0.026418, χ² =5.36, significantly more frequent compared with group III) in group I, in 92.3% (F= 0.006183, χ² =7.75 significantly more frequent compared with group III) in group II, and in 60% in group III. TT genotype was not detected in any group.

Conclusion. The identified features confirm the more favourable nature of the tumour process in iris melanomas compared to choroidal melanomas.

Сlear cell renal cell carcinoma (ccRCC) is a heterogeneous aggressive disease with a high mortality rate, so the search for risk markers is a relevant task. The material for the study was 128 DNA samples of ccRCC patients and 134 healthy individuals. It was revealed that the risk markers for ccRCC are rs11263432*T and rs793096*T alleles (OR=2.32 (95%CI=1.1–5.3) p=0.04 and OR=1.49 (95%CI=1.0-2.1) p=0.035, respectively).

Cas9-based genome editing methods may pose a risk when used in medicine because CRISPR/Cas9 systems are mutagenic, capable of introducing single- and double-strand breaks in DNA in both target and non-target regions of the genome, leading to unwanted mutations at the break site. The non-target activity of the editing complex is due to its ability to recognize 20-nucleotide sites in the genome that are not fully complementary to its guide RNA and introduce a double-strand break. In this study, we used the yeast Saccharomyces cerevisiae as a model organism to evaluate the effect of mismatches at different positions of the guide RNA on the editing efficiency of Cas9.

In Krasnodar region, neonatal screening (NS) for congenital adrenal hyperplasia (CAH) has been carried out since 01.06.06. In connection with the transition in 2023 to early blood sampling in newborns (the first 24-48 hours instead of 4-5 days of life), the assessment of the NS results for CAH was of interest. Over 24 years, 1,145,400 newborns were examined, 119 children with CAH were identified (1:9625). The 17OHP level above the threshold was determined in 1.4% of newborns. In 2023, the number of children who needed a retest increased to 2.1%. According to the NS data, in 2023-2024, the threshold level of 17OHP for newborns examined in 24-48 hours of life, increased by 4 nmol/l. The evaluation of the NS results with this threshold level in 2024 led to a decrease in the retest to 1.1%. In children with CAH, 3 common mutations of the CYP21A2 gene were detected: E3del (23.5%), I2spl (21.8%), I172N (16.8%). Changing the timing of newborn examination during NS requires monitoring the threshold levels of 17OHP to prevent unjustified retests.

Increased life expectancy during physiological aging and in age-related pathologies development is due to specific adaptive mechanisms, including individual genetic profile. With the aim to investigate the molecular-genetic bases of longevity, the sample of 3265 unrelated individuals aged 18–114 years from of the Republic of Bashkortostan, the survival under pathologies conditions and in healthy aging was analyzed. Polymorphic variants of thirty genes of cellular homeostasis were selected as the predictors. Markers of survival and agerelated adaptation to cardiovascular diseases (PON1 rs662, NFE2L2 rs6721961, AKT1 rs3803304, HIF1A rs11549465, TEAD1 Ya5ac2013), cerebrovascular pathologies (PON1 rs662, SEMA6A Yb8NBC597, GPX1 rs1050450), cancer (MTHFR rs1801133, SOD1 rs2070424, CAT rs1001179), diabetes mellitus and multimorbidity (SIRT1 rs3758391, LAMA2 Ya5-MLS19) were identified. The genetic predictors of survival in physiological aging were NFE2L2 rs6721961, KEAP1 rs1048290, and AKT1 rs3803304. Thus, genes involved in redox regulation, antioxidant protection of lipids, cell proliferation and activity, autophagy and apoptosis are associated with survival and longevity.