Atopic dermatitis is a chronic inflammatory multifactorial skin disease, the leading role in the development of which is played by dysfunctions of the skin protective barrier and imbalance of the immune system. It is known that the presence of loss-of-function variants in the filaggrin gene, leading to the formation of premature stop codons and translation of a truncated form of the protein, is one of the main risk factors for the development of atopic dermatitis. The literature review describes the importance of filaggrin protein in the formation of the epidermal barrier and the development of immune responses in the skin. Data on the frequency of filaggrin variants in the population and in patients with atopic dermatitis in different countries are presented. The most frequent loss- of-function variants among atopic dermatitis patients from Europe - c.2282_2285del, c.1501C>T, c.9740C>A and c.7339C>T - are rarely found in Asian countries, which are characterized by variants c.3321del, c.5101C>T, c.7661C>G, c.8666_7CC>GA and c.9887C>A. Based on the analysis of the results of case-control studies conducted among atopic dermatitis patients from Russia, it was shown that the only variant associated with the disease is the c.2282_2285del deletion, occurring in 11.8-26.6% of patients. The influence of filaggrin gene variants on the development and course of atopic dermatitis was characterized: age of onset and severity of the disease course, clinical features, development of concomitant allergic and infectious diseases, influence on the effectiveness of therapy.

Background. Attention to rare diseases is increasing more and more, especially in the decade. However, data on patient enrollment and prevalence of rare nosology associated with the occurrence and development of orphan disease registries.

Aim: analysis of the epidemiological data of group Russian patients with epidermolysis bullosa (EB) according to the data of the register of the charitable foundation «BELA. Butterfly Children» (BF).

Methods. An analysis of the age and sex characteristics of the patient’s group was carried out and presented with summarizing data for federal districts, the number of patients with molecular genetic results. Mortality index is provided, indicating the type of EB and the age of death of patients included in the BF Register. The prevalence of EB of all types together and each with exceptions per 1 million population was calculated.

Results. The article presents epidemiological and demographic data of 548 patients with EB from the BF Register. The prevalence of EB in the RF was 3.77 per 1 million population, which is significantly lower than in other populations. EB patients were represented by all age-related diseases living in 75 regions of the RF, most of which were in children under 18 years of age – 76%. The dominate nationality among patients was Russians – 56.7%. The distribution according to the main EB types was as follows: dystrophic EB – 59%, simplex EB – 30%, junctional EB – 6%, Kindler syndrome – 2%, unspecified EB – 3%. The coverage of molecular genetic studies was 86%. The presence of palliative status and disabled status in patients with EB was assessed, the presence of which was registered in 9.7% and 55.3%, respectively.

Conclusions. The obtain data will make it possible to correctly plan diagnostic, therapeutic, rehabilitation and preventive measures for each federal district of the Russian Federation, taking into account the local distribution of patients with the main types of EB and the severity of their course. The analysis of information from the registers of patients with rare diseases is an effective tool necessary for practical public health and scientific purposes.

Aim: to investigate the association of ZNF350 (rs2278420, rs2278415, rs4986773) gene polymorphisms with the risk of uveal melanoma development.

Methods. The study involved 226 volunteers who signed an informed consent, including 65 patients with UM and choroidal nevi (study group). According to the results of the clinical and instrumental examination, all patients were divided into two groups – a study group (patients with uveal melanoma and progressive choroidal nevus, n=42) and a risk group (patients with benign choroidal nevus, n=23). The control group (n=61) included individuals without intraocular neoplasms. The population group included Russian individuals (according to the survey data) randomly selected in Moscow. Genotyping for the ZNF350 rs2278415, rs2278420, and rs4986773 gene polymorphisms was carried out by PCR followed by DNA restriction.

Results. Comparing the allele and genotype frequencies for the ZNF350 rs2278415 and rs4986773 gene polymorphisms, no statistically significant differences were found between the studied groups. In the control group, the genotype AA and allele A for the ZNF350 rs2278420 gene polymorphism were determined significantly less frequently than in the study, risk, and population groups.

Conclusion. Our study has revealed, the AA genotype and A allele at the polymorphic locus rs2278420 of the ZNF350 gene are associated with UM, progressive, and benign choroidal nevi. Additionally, the higher frequencies of the genotype and allele found in the population sample may be related to the «random sampling» effect and insufficient information of their tumor family history.

The article presents the results of a combined (mixed) empirical study of attitudes of newborns’ mothers’ toward whole exome testing in neonatology, conducted in 2021-2022 at the «National medical research center for obstetrics, gynecology and perinatology named after academician V.I. Kulakov». The study involved questionnaires of 328 women and 31 semi-structured in-depth interviews with some of them. The study revealed a significant interest of respondents in neonatal genetic testing, which correlates with high trust in scientific knowledge in the field of medical genetics, achievements and discoveries in the field of science and technology. The development and expansion of genetic testing programs in neonatology requires the formulation of informing criteria, taking into account the degree of risk, availability of treatment and other factors. Also, further research is required to assess the risk of specific diseases, which will make it possible to apply the achievements of genetics not only for diagnosis and prevention, but also for family planning.

The clinical observation of the patient and a brief review of the literature on this problem (diagnosis and treatment) are given. Cerebral vascular thrombosis is one of the most common causes of death. The identification of the etiology of the disease is relevant for the tactics of treatment and prevention of thrombosis. The causes of cerebral vascular thrombosis, including in children, may be hyperhomocysteinemia, mutations in the genes of thrombophilia. The clinical observation of a 15-year-old child with deep vein thrombosis of the brain, venous sinuses is described. Tandem mass spectrometry and targeted sequencing were performed. A twofold increase in the level of homocysteine and methionine in the blood serum was determined. When sequencing the CBS gene (cystathionine beta-synthase gene) a mutation described in the international mutation database HGMD(CM970234) NM_000071 has been identified:c.785 C>T (p.T262M) in a heterozygous state. A replacement in the CBS gene NM_000071:c. 352 G>A (p.V118M), undescribed in the international database for HGMD mutations and dbSNP polymorphism, was also identified, but according to pathogenicity programs it is highly likely pathogenic. Conclusion: cerebral vascular thrombosis in children is a rare condition, so it is important to search for the genetic cause of the disease.

We report a clinical case of the patient with a rare phenotype presented by progressive cerebellar ataxia in combination with upper and lower motor neuron involvement. Target panel sequencing revealed the previously described pathogenic mutation c.272A>C (p.D91A, rs80265967) in the 4th exon of the SOD1 gene. Mutations in this gene are a common cause of the hereditary forms of amyotrophic lateral sclerosis (ALS, MIM #105400). The combination of ALS with cerebellar ataxia is an extremely rare, and cases of association of this mutation with cerebellar ataxia have not been previously described. The presented clinical observation and literature data expand the understanding of the genetic and phenotypic “overlap” of hereditary ataxias and motor neuron diseases. The development of drugs for SOD1-ALS gene therapy, including the use of antisense oligonucleotides aimed at suppressing SOD1 gene expression, is currently underway. In this regard, it is necessary to include the study of the SOD1 gene in the algorithms for diagnosing hereditary cerebellar ataxia in the presence of a characteristic clinical phenotype.