Niemann-Pick disease type A/B is lysosomal storage disease caused by acid sphingomyelinase (ASM) deficiency. The accumulation of sphingomyelin in cells causes damage to various organs, such as the liver and central nervous system. Symptoms of this disease include hepatosplenomegaly, neurological deficiency, and lung disease. There are three main forms of the disease: type A, type B, and intermediate type A/B. Type A is characterized by severe neural degeneration and prominent neurological deficit, while type B is milder with minimal neurological manifestations and signs of lipid accumulation. The intermediate type combines features of both types of Niemann-Pick disease. The diagnosis of Niemann-Pick disease types A/B is made using laboratory tests and results, including ASM activity assessment and genetic mutations in the SMPD1 gene. The gold standard is the enzyme activity assay on dry blood spots. Treatment mainly consists of enzyme replacement therapy (ERT), which improves the condition of the patient, although its effectiveness in neurological symptoms is limited. Alternative methods such as bone marrow transplantation, gene therapy and molecular chaperone therapy are currently being investigated. Despite the advances in the understanding of the pathogenesis and therapy of Niemann-Pick disease types A/B, further investigations are needed to advance early diagnostic methods and develop new therapeutic approaches, especially in the field of gene technology.

Brugada syndrome (BrS) is an inherited cardiac disorder characterized by specific electrocardiogram (ECG) abnormalities and a high risk of ventricular arrhythmias and sudden cardiac death. BrS is more common in young men and its clinical manifestations range from asymptomatic cases to sudden cardiac death. Epidemiological data show significant regional and ethnic variation in the prevalence of BrS, with the highest incidence in Southeast Asia. Investigation of the genetic factors of BrS is critical to understanding the pathogenesis, developing diagnostic and prognostic methods, and targeted therapeutic approaches. The major genes associated with BrS include SCN5A, CACNA1C, CACNB2, SCN1B and SCN3B. These genes encode ion channels, and their pathogenic variants can lead to significant electrophysiological disturbances, resulting in arrhythmias and sudden cardiac death. Modern genetic testing methods, such as next-generation sequencing (ngs), play a key role in identifying genetic mutations associated with brs. These technologies allow for improved diagnostics and risk prediction, as well as the development of individualized treatment plans based on the patient’s genetic profile, improving the prognosis and quality of life of patients with this disease.

For the first time, a comparative study of the characteristics of the ribosomal gene complex (rDNA) in the blood cells of patients with catatonic and paranoid schizophrenia and a control sample was conducted. The study involved patients with schizophrenia who live in Moscow and the Moscow region and were treated for an exacerbation of the disease at the N.A. Alekseev Psychiatric Clinical Hospital No. 1 of the Moscow City Health Department. Two groups were formed: catatonic schizophrenia (N 124); diagnosis (ICD-10): F20.2; a group of patients with the paranoid form of schizophrenia (N 450), (F20.0) and a control group (N = 240) – mentally healthy people. The level of rDNA and nuclear DNA damage (flow cytometry), the number of rDNA copies in a cell (non-radioactive hybridization), the level of rDNA transcription and the amount of 18S rRNA (RT-PCR) were determined. Catatonia is associated with higher levels of rDNA and DNA damage and higher levels of rDNA and 18S rRNA in the blood cells of patients. It is suggested that increased levels of ribosome biogenesis, including higher levels of rDNA copies in the cells of patients with catatonia, are necessary for an effective response to higher oxidative stress.

Mucopolysaccharidosis-plus syndrome (MPSPS, OMIM # 617303) – is a rare autosomal recessive inherited disorder caused by a c.1492C>T mutation in exon 12 of the VPS33A gene. The disease is characterised by a ‘gargoylism’ phenotype, including skeletal anomalies, heart damage, joint contractures, delayed psychomotor and physical development, and additional disorders of the kidney and haematopoietic system. The clinical picture of MPSPS was initially delineated by the medical team at the Medical and Genetic Centre of Yakutsk in 2014, and the underlying molecular genetic cause was subsequently identified in 2017. In the paper, a ‘founder haplotype’ of the MPSPC locus was established through linkage disequilibrium analysis of 11 microsatellite markers, indicating the accumulation of the mutation as a result of the founder effect. The time of spread of the mutation in Yakutia was determined to be 2312 ± 1375 years. The average value of the number of generations that have passed since the beginning of the spread of the c.1492C>T mutation in the Yakut population was found to be 92,5.

Introduction. Accumulated data show that microRNA plays a crucial role in almost all biological and pathophysiological processes, such as cell cycle regulation, cell differentiation, lipid metabolism, neurological, cardiovascular and metabolic diseases and cancer, including melanoma.

Aim: to search for associations between polymorphic variants MIR146A (rs2910164), MIR758 (rs1885068), MIR33a (rs9620000) and the risk of melanoma.

Methods. Paraffin blocks of 82 people with melanoma and peripheral blood of 35 donors of the control group were used as the material for the study. DNA was used from paraffin block sections (FFPE) using a commercial QIAamp DNA FFPE Tissue Kit (QIAGENE, Germany). Primers for PCR were selected using the WASP program. Genomic DNA is popular with the QIAamp DNA Blood mini kit (Qiagen, Germany). Genotyping of animals using the allele-specific PCR mixture qPCRmix –HS (Eurogen, Russia) on the Real-time CFX96 Touch (USA). Analyze the Hardy-Weinberg equilibrium and differences in the distributed alleys of variants between experimental patients and control measurements using the χ2 criterion. To assess the risk of developing melanoma, we used odds ratios (OR).

Results. The study found that the allele A of the MIR146A gene (rs2910164) (OR = 2.24, 95% CI = 1.24–4.03; p = 0.02) and the TT genotype of the MIR33a gene (rs9620000) (OR = 2.98, 95% CI = 1.17–7.60); p = 0.03) are associated with an increased risk of melanoma. The presence of a polymorphic allele of the MIR758 gene (rs1885068) is not associated with the development of melanoma.

Conclusion. Thus, the results of the study emphasize the depth of the search for diagnostic biomarkers in the non-coding region of the genome.

The medical records of 1381 families burdened with hereditary pathology from the archive of the Laboratory of Genetic Epidemiology of the Research Centre for Medical Genetics in rural population of Karachay-Cherkessia and North Ossetia-Alania were analysed. The birth rate in these families is considered, taking into account the ethnicity. Both a general estimate of birth rate and separate estimates for families with autosomal dominant and autosomal recessive pathology were obtained. A comparison with the population assessment was carried out. Despite a slight decrease in the birth rate in burdened families, especially for AR pathology, the preservation of birth rate in burdened families was noted.