Tuberous sclerosis is an orphan autosomal dominant hereditary disease caused by inactivating mutations in the TSC1 or TSC2 genes, accompanied by hyperactivation of the mTOR signaling pathway, which is responsible for the regulation of growth, proliferation, cell survival, and autophagy. One of the main clinical symptoms of tuberous sclerosis is the formation of tubers in the brain. These formations are characterized by disorders of the cortical lamination, the appearance of abnormal neurons and severe gliosis. It is known that the presence of cortical tubers correlates with the development of neuropsychiatric disorders, including drug-resistant epilepsy. This article highlights the issues of molecular genetics of tuberous sclerosis, presents the histopathological characteristics of cortical tubers, considers mechanism of morphogenesis of cortical tubers, and also presents the data on relationship of these formations with the development of neurological manifestations and methods of their treatment.

Mutations in the SLC26A4 gene can lead to both the formation of autosomal recessive deafness type 4 (DFNB4, OMIM#600791), and to Pendred’s syndrome (PDS, OMIM#274600), in which sensorineural hearing loss is combined with thyroid dysfunction, with both forms can be accompanied by specific anomalies of the inner ear: IP-I, IP-II (Mondini) and/or EVA. Using audiological, radiological and molecular genetics methods, 165 patients with congenital hearing impairment in Yakutia were examined. Computed tomography revealed IP-I, IP-II (Mondini) and/or EVA abnormalities in 9 of 165 (5,5%) patients. Then, using direct Sanger sequencing in these 9 patients, the nucleotide sequence of the coding regions of the SLC26A4 gene (21 exons) was determined. In total, 5 previously known variants were found in the SLC26A4 gene, among which 4 variants were missense substitutions: c.85G>C p.(Glu29Gln), c.441G>A p.(Met147Ile), c.757A>G p.(Ile253Val), c.2027T>A p.(Leu676Gln) and one variant affected the splice donor site - c.2089+1G>A (IVS18+1G>A). In 4 out of 9 patients, pathogenic variants of the SLC26A4 gene were found in a homozygous or compound heterozygous state. The total contribution of biallelic mutations in the SLC26A4 gene among patients with inner ear anomalies was 44,4%. Patients with biallelic SLC26A4-mutations had several to profound bilateral sensorineural hearing loss. In patients with biallelic SLC26A4-mutations, the dominant type of anomaly was IP-II (Mondini)+EVA (62,5%), IP-I anomalies were not detected in any patient. In three patients we were able to confirm the diagnosis of DFNB4, and in one patient, due to the sum of phenotypic features (operated on for nodular goiter, autosomal recessive deafness with EVA), Pendred’s syndrome was diagnosed.

Background. Environmental pollutions, toxic agents and dangerous radiation lead to increasing in levels of mutational processes, DNA damages and higher risks of cancer for bioorganisms. The life system viability depends on the effectiveness of the neutralizing the adverse factors. The unavoidance of the DNA damaging factors has led to developing the effective repair systems aimed to eliminate the primary damage. 8-oxoguanine-DNA glycosylase (OGG1) is the major element of the Base Excision Repair (BER) in human. The OGG1 gene has coding sequence variations spread with different frequencies in human populations. Ser326Cys is SNP with known defect in DNA repairing for Cys-allelomorph and an increased risk of cancer in the case. Objective. The study was aimed to estimate the prevalence OGG1 gene variants among the indigenous Abkhazian population and comparison with different ethnic groups worldwide. Methods. The study based on the analysis of 168 samples from Abkhazians. The OGG1 gene Ser326Cys genotyping was performed by the ARMS-PCR-RFLP . Results. The frequency stated for Ser/Ser genotype was 44.1%, Ser/Cys = 49.4 % and Cys/Cys = 6.5% in the Abkhazian population. Frequency of the OGG1 allele*C (Ser) was equal to 0.688, and OGG1*G (Cys) reached the value of 0.312. Conclusion. The frequencies of the rs1052133 alleles in the Abkhazian population were close to the global average values.

Single-gene microduplication of the TSPAN7 gene is often classified as either a rearrangement of uncertain clinical significance or likely pathogenic, although other clinical features are often observed in hemizygous carriers in addition to intellectual disability or autism. This is characteristic of syndromic intellectual disability. In this study, we analyzed the pathogenetic significance of the microduplication in the XLID phenotype in two patients.

The results of the expert assessment of the quality of cytogenetic studies in the laboratories of the Russian Federation in the system of interlaboratory comparison tests «FSVOK» for 2020 are presented.

Aim: we report of our data of successful preimplantation genetic testing (PGT-M) for mucopolysaccharidosis type II (MPS II, Hunter syndrome). Methods. A couple (32 and 31 years old) with Hunter syndrome affected child asked for PGT-M for MPS II (pathogenic variant c.613delG of the IDS gene). In addition, the woman has an inversion of chromosome 10. A system of targeted preimplantation testing was developed for the family, validated on single lymphocytes and whole genome amplification products.. Nested PCR method and fragmentary analysis were used for molecular genetic studies. Two IVF (in vitro fertilization) programs was carried out. Standard protocols for controlled ovarian hyperstimulation with fertilization by ICSI (intracytoplasmic sperm injection) were used. Embryo biopsy was performed on the 5th day of embryo development (day 6th for one embryo), embryos were vitrified. Transport PGT-M (PGT for monogenic/single gene defects) was carried using system created at pre-examination setup. Prenatal diagnosis was performed using the chorion villus biopsy method; karyotype, IDS gene and fetal sex were analyzed. Results. During setup, 14 STR (short tandem repeat) markers linked to the IDS gene were selected and tested, half of them were informative and acceptable for single cells. Developed for the family the PGT-M MPS II system included analysis of a pathogenic variant of the IDS gene, seven informative STR markers, AMEL and SRY genes. No PGT-A (PGT for aneuploidy) was carried out. In the first IVF program, three embryos were tested and recommended for transfer, but the transfer was postponed at the patient request. In the second IVF program, five embryos were tested, three recommended for transfer. Frozen single embryo transfer of normal male embryo at the second of IVF-PGT-M program was carried out. A singleton pregnancy was achieved. Prenatal diagnosis fully confirmed PGT-M results. A healthy boy was delivered in July 2021. Conclusions. The successful implementation IVF-PGT-M with developed system and good reproductive potential of the couple made it possible to achieve pregnancy and the birth of a healthy child in a family with a high genetic risk for MPS II.