We investigated the effort of fullerene derivative with five attached residues of 3-benzothienylalanine and one hydrogen atom (F1) on the functioning of the human embryonic lung fibroblasts (HELF). It was shown that F1 penetrates the cytoplasm of most cells in the population within 24 hours. To study the effect of F1 on HELF, two concentrations were selected: 18.3 ng/ml, which is in the range of non–toxic concentrations and a concentration close to damaging – 28 µg/ml and three incubation times of cells with compounds – 1, 3 and 24 hours. It was found that after 24 hours in the presence of low concentrations of F1, the level of ROS in cells decreases, which is due to an increase in the expression of the NRF2 gene and an increase in its functional activity. The F1 compound in a concentration close to toxic causes an increase in the expression level of the NOX4 gene and protein in cultured HELF, which leads to the synthesis of ROS in cells and oxidative modifications, and double-stranded DNA breaks of cell nuclei after 24 hours of incubations. There was no effect of F1 on the expression level of the BRCA1 gene and protein, which probably contributes to the formation of double-stranded DNA breaks in cells and maintenance at a high level after 24 hours of incubation. An increase in the expression of anti-apoptotic genes in HELF after 24 hours of cultivation with F1 may contribute to the survival of cells with damaged DNA.

   Duchenne muscular dystrophy (DMD) is the most common neuromuscular disease in the world. DMD belongs to the group of so-called dystrophinopathies associated with mutations in the DMD gene, is inherited in an X-linked recessive manner and is caused by either the complete absence of the dystrophin protein or its defective synthesis. Currently, several pathogenetic drugs have appeared aimed at restoring the synthesis of the dystrophin protein. One of them is the antisense oligonucleotide casimersen, which works using exon skipping technology of exon 45 in DMD gene. The article presents the first experience of using the drug casimersen in 6 patients from Russia, and the patients differed significantly from each other in functional status and existing complications of the underlying disease. In all patients, the use of casimersen was safe, and no adverse events associated with the use of the drug were identified. And in one of the patients, who was at an early outpatient stage of the disease, for whom pathogenetic therapy was initiated at the age of 7 years, pronounced positive dynamics were noted in the form of an increase in distance by 140 meters according to the results of a 6-minute walking test and an increase of 10 points on the «North Star».

   Introduction. Klinefelter syndrome (KS) is a sex chromosome abnormality characterized by high prevalence in various populations, hypergonadotropic hypogonadism, male infertility, pronounced clinical variability of symptoms and commonly late diagnosis. The causes of phenotypic variability of KS, including the influence of genetic, epigenetic and environment factors on it, is still not well understood.

   Aim: evaluation of the CAG polymorphism of androgen receptor (AR) gene and the parental origin of the X chromosomes on clinical and laboratory parameters in Klinefelter syndrome patients.

   Methods. We examined 34 KS patients 5-18 years of age with following karyotypes: 47,XXY (n = 32); 48,XXYY (n = 1) и mos 47,ХХY[22]/46,XY[8] (n = 1). Two patients were monozygotic twins, the other patients were unrelated. Parental origin of the X chromosomes was determined by genotyping for (CAG)n polymorphism of the AR gene and (GAAA)n polymorphism, near to the RP2 gene, in patients and parents. The influence of the origin of the additional X chromosome and CAG-repeats of AR gene on the clinical and laboratory parameters was assessed in 22 adolescents with a karyotype 47,XXY, who had reached the Tanner stage of sexual development ≥2, and not received testosterone replacement therapy at the time of examination.

   Results. The number of CAG repeats of the AR gene in KS patients was ranged from 16 to 27, and 22 alleles (32.4%) contained from 20 or 21 repeats. According to CAG-repeats, a group of 22 adolescents with KS was divided into 3 subgroups: carriers of “short” alleles ((CAG) n ≤ 19; 6 patients), “medium” alleles ((CAG) n = 20–25; 12 patients) and “long” alleles ((CAG)n ≥ 26; 4 patients) alleles. Comparative analysis of anthropometric data (SDS of height and BMI, ΔSDS of body segments) did not reveal statistically significant differences between subgroups. In the group of carriers of “long” alleles, higher levels of testosterone and insulin and a larger testicular volume were noted compared to carriers of “medium” and “short” alleles. The study groups also did not differ in the levels of gonadotropins (LH, FSH) and metabolic profile indicators (total cholesterol, LDL, HDL, TG). The parental origin of the additional X chromosome was established in 33 patients, of which 22 (67 %) patients had maternal origin (Xm), and 11 (33 %) individuals had paternal origin (Xp). Analysis of the influence of the origin of the X chromosome on anthropometric indicators, hormonal and lipid profiles in 22 adolescents selected for the study (additional Xm, n=15; additional Xp, n=7) did not reveal statistically significant differences between the subgroups. No significant influence of the parental origin of the additional X chromosome and the CAG polymorphism of the androgen receptor gene on clinical and hormonal-metabolic parameters in our sample of KS patients, was found.

   In discussions about the origin of the largest tribal group of Tuvans, the Mongush (57 thousand people), two alternative hypotheses prevail. The «Mongolian» version traces their ethnogenesis back to the Mongols (or to the newcomer population from Central Asia). The «Turkic» hypothesis connects their origin with the local autochthonous population who switched to the Turkic language.

   The purpose of this work is to study the gene pool of two subgroups of the Mongush (central and western) using the detailed structure of the Y-chromosome and an enlarged sample, to determine the degree of their genetic similarity to each other, with the gene pools of other Tuvan tribal groups, populations of Southern Siberia and Mongolia.

   Genogeographic analysis of 187 individuals of 4 tribal groups of Tuvans (Mongush, Oorzhak, Khertek, Sat) using a panel of 60 SNP markers of the Y chromosome included the creation of distribution maps of the most informative haplogroups of the Y chromosome; calculation of genetic distances between the tribal groups of Tuvans and the population of Southern Siberia and Mongolia; creation of maps of genetic distances from each tribal group of Tuvans. In the gene pools of 4 Tuvan tribal groups, 46 informative Y-chromosome haplogroups were identified: «North Eurasian» N, Q; «Western Eurasian» R1a; «East Eurasian» C2, D, O; «other» R2a, R1b, J2. In all tribal groups, both «Western Eurasian» and «East Eurasian» haplogroups do not exceed 13-20% of the gene pool. «North Eurasian» haplogroups make up the bulk (60-63%) of the gene pools of all genera, but in different proportions. Haplogroup N is maximum in Oorzhak and Mongush (western) – 2/3 of the gene pool and 1/3 of the gene pool of the Mongush (central), Sat and Khertek tribal groups. The opposite trend is observed for haplogroup Q: 30 % of the gene pools are Sat and Khertek, 20 % Mongush (central), 7 % Oorzhak and Mongush (western). In the genetic space of Southern Siberia, Tuvan-Tofalar, Altai and Khakass clusters have been identified, demonstrating three ancestral sources of the gene pool of the region. The cartographic atlas revealed the similarity of the western and central Mongush with other Tuvan tribal groups, indicating the unity of origin of the four Tuvan tribal groups. The predominance of «North Eurasian» haplogroups N and Q in the gene pools of both groups of Mongush confirms the hypothesis of their formation on the Samoyed-Ket layer (VI-III YBC) and the «Turkic» hypothesis of ethnogenesis with an extremely weak influence of the Mongol-speaking component on Tuvan ethnicity.

   The meta-analysis was aimed to evaluate the association between polymorphisms rs2107425, rs2839698, rs217727, rs3741219 of the H19 gene and the risk of developing of breast cancer. Publications were searched in the Google Scholar and PubMed databases until August 2023. The association was assessed by statistical odds ratio (OR) criteria with a 95% confidence interval (CI). RevMan software (Cochrane Collaboration, 5.3. Copenhagen) was used for the meta-analysis. To assess the association of polymorphisms rs2107425, rs2839698, rs217727, rs3741219 with the risk of developing breast cancer, 9 case-control studies with a total sample of 6572 patients with breast cancer and 6968 donors in the control group were included in the meta-analysis. As a result of the study, we observed an association between rs2839698 H19 and the risk of developing breast cancer when calculating the allelic model (OR = 1.33, 95 % CI: 1.00-1.76, Pz = 0.005, Pi2 = < 0.00001). In addition, analysis of the recessive model also showed that the risk of developing breast cancer was significantly associated in individuals with a mutation in the polymorphic allele rs2839698 (OR = 1.33, 95 % CI: 1.03-1.71, Pz = 0.03, Pi2 = 0.05). When calculating genetic models for the rs2107425, rs217727, rs3741219 polymorphisms, no statistically significant associations with the risk of developing breast cancer were found. The present meta-analysis showed that the H19 rs2839698 polymorphism associated with the risk of breast cancer.

   The study of rare variants in the CFTR gene is relevant in the era of targeted therapy with CFTR modulators. In this study, we studied the clinical picture of cystic fibrosis, as well as the function of the CFTR channel in a homozygous carrier of a rare pathogenic variant c.1329_1350del (p.Asp443GlufsX19), belonging to class I disorders in the CFTR gene. A complete correlation of the results of functional tests with the phenotypic pattern of CF and data of a sweat test was obtained. The method for determining the difference in intestinal potentials demonstrated the absence of functional activity of the chloride CFTR channel in the rectal biopsy, and when stimulated with forskolin, the patient’s organoids did not swell, which indicates a complete violation of the functional CFTR protein production. Exposure to intestinal organoids by all registered for therapy targeted drugs did not lead to their swelling, unlike the control culture, homozygous for F508del. The chloride channel of a patient with genotype p.Asp443GlufsX19/p.Asp443GlufsX19 turned out to be insensitive to any CFTR modulator.