Epithelial-mesenchymal transition (EMT) is the basis of tumor invasion and metastasis. It is characterized by the loss of communication between epithelial cells, which lead to the appearance of a motile phenotype of mesenchymal cells. The E-cadherin protein plays an important role in the EMT process, establishing and maintaining intercellular interactions and allowing epithelial cells to form a cell layer. The partial or complete loss of E-cadherin expression that occurs during EMT is mediated by mechanisms that block the expression of activators of this protein and related transcription factors. In contrast, the inhibitors of E-cadherin SNAIL1/2, ZEB, TWIST1, GRHL2, OVOL1/2, and PRRX1 are overexpressed. E-cadherin is involved in various oncogenic signaling pathways such as Wnt/β-catenin, Rho GTPase and EGF/EGFR. Therefore it contributes to many tumors, including gastric cancer (GC). MicroRNAs and long noncoding RNAs as important epigenetic regulators of gene expression in carcinogenesis are also involved in the regulation of E-cadherin function. They act directly or indirectly, through multiple factors controlling gene transcription, and thus influence tumor cell proliferation and metastasis. This review is focused on the role of E-cadherin in tumor progression and the involvement of non-coding RNAs in the mechanisms controlling its expression in gastric carcinogenesis.

Treatment of many of the diseases in the panel of expanded newborn screening includes dietary therapy. Hereditary tyrosinemia type I (HT-I) is inherited metabolic disease caused by defects in tyrosine metabolism and by a mutation in the gene coding for fumarylacetoacetate hydrolase (FAH). The main clinical features of HT-I are caused by hepatic involvement and renal tubular dysfunction. The recommended treatment approaches for HT-1 are the prescription of specialized nutrition products, pharmacologic treatment with nitisinone, a peroral inhibitor of FAH in the tyrosine catabolic pathway, and symptomatic management. Dietary intervention with restriction of phenylalanine and tyrosine together with supportive measures can ameliorate the symptoms, but given the high risk for hepatocellular carcinoma, a cure for these patients so far is possible only with liver transplantation. In 2021, clinical guidelines for the treatment of this rаre disease were published in Russian Federation. To provide for the timely treatment, it is essential for a practitioner involved in the care patients with such a rare disorder as НТ-1 to have the knowledge of the principles of management, as well as practical algorithms for diet calculation. The article gives a detailed case-based description of management during metabolic decompensation and the choice of dietary therapy for HT-1 patients of different age groups.

Aim: to present a technique for prenatal molecular genetic diagnosis (PD) of congenital adrenal hyperplasia (CAH), including test of common pathogenic CYP21A2 variants, linkage microsatellite markers and sex markers analysis. Methods. DNA samples were isolated from whole blood samples and chorionic villi sample. The research based on methods from literature and own developments. The assay included the analysis of common mutations in the CYP21A2 gene (P30L, IVS2AS A/C-G,-13, 8 bp del, I172N, V281L, Q318X, R356W, P453S), gene-pseudogene rearrangement (deletion of 30 kb), STR markers (TNFa, D6S273, D6S2781, LH1, D6S1666, D6S2443) and sex markers (SRY and AMELX/AMELY). PCR was baseline method for all steps. We performed a nested PCR approach and subsequent restriction analysis for point mutations of the CYP21A2 gene. Methods of gel electrophoresis and fragment analysis on a genetic analyzer were used for detection. Results. Our study describes the detailed approach of prenatal molecular genetic investigation of CAH. Preliminary molecular genetic examination of a family with a salt-wasting form of CAH child was carried out. A compound genotype with pathogenic maternal variants IVS2AS A/C-G, -13 and a complex mutant paternal allele P30L + 8 bp del + IVS2AS A/C-G, -13 was revealed in the affected child. In the fetal sample we identified a heterozygous genotype with a pathogenic maternal allele of the 2nd intron. The polymorphic microsatellite markers flanking the CYP21A2 gene confirmed the normal paternal and pathogenic maternal haplotypes in the fetus. Additionally STR data indicated that there was no contamination of maternal DNA fetal material. The mother was uninformative (homozygous) with two microsatellite markers, the father was informative with all six. Conclusions. We devised an improved stepwise molecular diagnostic strategy includes the direct analysis of pathogenic variants in combination with indirect diagnostics by STR markers and sex analysis for reliable PD of CAH.

The study of the genetic structure of the North Ossetian Kumyks is carried out as part of a genetic and epidemiological survey of the population of the Republic of North Ossetia-Alania. Kumyks compactly live in Mozdoksky district and present 18% of district population. Based on the marriage records for 1990-2000, the main population genetic parameters of the North Ossetian Kumyks were determined. Malekot’s parameters of isolation are Ne=4220, σ=35.6, a=0.00067, b=0.0277. The territorial endogamy index is 0.86. Ethnic marital assortativity is 3.3. The intensity of mestization is 17.6%. Effective fertility is 2.94±0.17. The total Crow index is 0.214, and its components Im=0.048, If=0.159.

A case of type 1 tyrosinemia in a newborn is presented with a description of clinical signs illustrating the complexity of diagnosing the disease in a newborn. Particular attention is paid to the description of neurological manifestations and the results of instrumental examination. The inclusion of type 1 tyrosinemia in expanded neonatal screening will reduce the time for diagnosing the disease in newborns and start pathogenetic treatment as early as possible.