Background. According to the frequency of occurrences dysferlinopathy occupies the second place in world among limb–girdle muscular dystrophy (LGMD) after calpainopathy. The disease has a relatively late manifestation and the similar clinical picture with other LGMD. In some cases, that creates significant difficulties in differential diagnostics. New generation sequencing (NGS) is method that quickly and efficiently allows to determine the variant of the DYSF gene that leads to violation of protein synthesis.

Aim: to determine the effectiveness of identifying variants of nucleotide sequences in the DYSF gene by the NGS in patients with aclinical diagnosis of diferlinopathy and also to evaluate the possibilities of this method in differential diagnostics of LGMD.

Methods. The search for genetic variants of the DYSF gene was performed in patients with detected phenotype of LGMD, as well as 10 to 100 times higher levels of creatine kinase (CK) and manifestation at the age of 2-73 years. In total, 157 patients with a clinical signs of LGMD were included in the study. Changes in the sequence of the DYSF gene were detected in 27 of them. 9 of 27 people – 34(15-58)% were examined with Sanger sequencing. 18 of them – 67(42-85)% were examined by the NGS method. In two patients only one changed variant in the DYSF gene was detected, in this regard multiplex ligation-dependent probe amplification (MLPA) was performed to search for large deletions and (or) duplications. The identified genetic variants were verified by the reference method – PCR. Histological and immunohistological examination was performed in four patients with ambiguous results. As a biopsy material for examination were used fragments (5 mm3) of the lateral head of the quadriceps femoral muscle.

Results and conclusions. Using the NGS method, in 27 patients 21 genetic variant of the DYSF gene was identified. 16 variants out of 21 belong to the category of previously described; thus, in almost a quarter of cases (5) – 25(0-52)% variants weren’t described before (novel). Among the 21 identified variants, based on ACMG criteria, 12 – 57(31-81)% variants were classified as pathogenic, 5 – 25(0-51)% as probably pathogenic and 4 – 20(0-46)% as variants with uncertain significance, however, all detected variants were accompanied by a detailed clinical signs of LGMD.

Objective: to assess the burden of isolated and syndromic forms of hereditary pathology of the organ of vision (HPOV) in a number of populations and ethnic groups of the European part of the Russian Federation.

Methods. A total of 3,195,054 people (17 populations (12 ethnic groups) living in 14 regions of the European part of the Russian Federation) were examined. The families were examined by doctors of various profiles specializing in hereditary pathology.  All patients underwent clinical, genealogical, laboratory, standard and special ophthalmological, as well as molecular genetic studies. According to the indications, perimetry, optical coherence tomography and electrophysiological studies were performed. The methods of molecular genetic analysis used included direct Sanger sequencing, MLPA, RFLP, AFLP, and full-exome sequencing. A comparative analysis of cargo between populations was carried out using the c2 test and the Student’s t-test.

Results. Among all patients, the proportion of patients with isolated forms of HPOV was 49% (1458 patients), syndromic – 51%(1539patients). The predominant type of inheritance is autosomal dominant (AD). The prevalence of isolated forms of pathology of the organ of vision is on average 1:2196 people, syndromic – 1:2076, the total prevalence of all forms of hereditary ophthalmopathology was 1:1066 people. The prevalence of HPOV among the Russian population (1:1,479 people) is more than 2 times lower than in the ethnic populations of the European part of the Russian Federation (1: 778 people). Significant differences were revealed in all types of inheritance and general burden for isolated HPOV (AD-I χ2=56.51; autosomal recessive (AR)-I c2=11.79; X-linked-I c2=28.58; Total-I χ2=84.92; p≤0.05; D.f.=1). When comparing the syndromic forms, the greatest differences were noted for the total load (AD-Sum χ216=56.51; AR-Sum χ2=11.79; ХR- Sum χ2=28.58; Total- Sum χ2=84.92; p≤0.05; D.F.=1).

Conclusion. The study indicates the presence of variability in the cargo of NPOs between populations and ethnic groups of the European part of the Russian Federation.

Gastric cancer (GC) is an aggressive tumor that is one of the leading causes of death from cancer. Treatment regimens are not often effective for this disease, so the development of new approaches to therapy and the search for predictive markers seems to be an urgent scientific task. Immune checkpoints (ICs) are promising therapeutic targets for malignant neoplasms. To understand the pathogenesis and optimize therapy, the role of ICs in tumor progression is being actively studied. In this study, IC gene expression levels and their co-expression with epithelial-mesenchymal transition-related genes were examined in a sample of patients with a microsatellite stable GC tumor phenotype. The association of the expression of these genes with the clinical characteristics of GC was assessed. It was found that the expression of the CD276 and PVR genes was reduced in low-differentiated tumors (p < 0.05). The development of metastases is associated with an increased level of TDO2 gene expression. In non-metastatic GC, a correlation was found between the expression levels of the CD44 and CD276 genes. In metastatic GC, a correlation of expression levels was found between the ADAM17, PVR, CD276 genes and the CD44, SNAI1 genes. The findings add to the understanding of the molecular genetic mechanisms that regulate tumor progression and may contribute to the development of new therapeutic approaches involving mutual inhibition of genes.

The aim of the study was to assess the prevalence of polymorphisms of the PNPLA3 (rs738409), HFE (rs1800562, rs1799945, rs1800730) genes in a group of patients with metabolic syndrome and non-alcoholic fatty liver disease living in the Krasnoyarsk Territory. In the course of the work, groups of patients with metabolic syndrome and non-alcoholic fatty liver disease (n=72) and practically healthy volunteers (n=83) were formed. The data of the frequency of polymorphisms were obtained and compared with global frequencies. DNA extraction was performed from whole blood leukocytes; RT-PCR was performed using hydrolysis oligonucleotide probes.

Results. In practically healthy volunteers living in the Krasnoyarsk Territory, there were no differences in the frequency of alleles and genotypes of polymorphisms of the PNPLA3, HFE, genes compared to Caucasians. In patients with metabolic syndrome and non-alcoholic fatty liver disease, a high prevalence of the mutant allele T and the AT genotype, alow frequency of the AA genotype of the HFE gene (rs1800730), and a low occurrence of the CG genotype of the HFE gene polymorphism (rs1799945) were found.

Background. Preimplantation genetic testing (PGT) is developing as a variant of early prenatal prevention of hereditary diseases. Targeted variant PGT for monogenic disease (PGT-M) involves a combination of pathogenic variant and indirect DNA markers analysis. The list of DNA markers linked to the CFTR gene for the purposes of cystic fibrosis PGT (PGT CF) varies by different authors.

Aim: development of a panel of STR-markers for PGT CF.

Methods Intragenic and extragenic STR markers linked to the CFTR gene were selected using scientific literature data and databases. The panel of markers was tested on DNA samples from seven families with CF, in which the disease is caused by the pathogenic F508del variant. Only one family had CFTRdele2,3(21kb) as the second mutation. For testing, PCR and fragment analysis methods were used.

Results. 15 main and 4 additional STR markers have been selected for a panel. Most of the samples of the parents carrying the pathogenic variant of the CFTR gene confirmed the sufficient information content of the main STR panel. An additional panel was required due to the fact that one of the studied samples revealed low information rate for linked markers because of a special haplotype of the chromosome carrying the normal allele.

Conclusions. The developed panel, taking into account the specific F508del haplotype, can serve as a basis for PGT CF.

Cutaneous-skeletal hypophosphatemia syndrome (CSHS) or Epidermal nevus syndrome (ENS) associated with hypophosphatemic rickets is a rare variation of hypophosphatemic rickets caused by phosphate wasting due to elevated fibroblast growth factor-23 (FGF23) as a result of somatic gain‐of‐function variants in the HRAS, NRAS, or KRAS genes. Clinical symptoms of CSHS, besides rickets, are congenital epidermal, melanocytic and sebaceous nevus as well as focal bone lesions ipsilateral to nevus. What makes genetic diagnosis of this condition extremely problematic is the necessity of location of mutations in the affected tissues (bones, epidermis). Such patients have a high risk of becoming disabled due to severe hypotonia, osteomalacia, bone fractures and difficulties associated with treatment of severe hypophosphatemia. The first two clinical cases of two unrelated patients with such condition have been performed in Russia. Both patients have CSHS confirmed by genetic testing.

At the request of the authors in the article Andreeva M.V., Kurilo L.F., Shtaut M.I., Chernykh V.B. «Partial block of spermatogenesis in two carriers of Robertsonian translocations (14;15)», published in the journal [Medical Genetics 2023; 22(4): 44-48], a change is made to the section «Funding»: The study was carried out within the framework of the state task of the Research Centre for Medical Genetics.