Childhood obesity is a major public health problem due to genetic and environmental factors. Despite significant advances in understanding the genetic basis of obesity, diagnosis and treatment of this disease in children remain challenging. This article focuses on semaphorins, a family of proteins that play an important role in the regulation of the leptin signaling pathway and are associated with early obesity. In addition, the publication outlines a review on the potential effects of semaphorins on appetite and metabolism, which may have implications for understanding the pathogenesis of childhood obesity. We emphasize the need for further investigation of semaphorins as potential markers and therapeutic targets in the fight against childhood obesity, which may help to improve the
diagnosis and treatment of this disease in children.

Disruption of epigenetic mechanisms of gene expression regulation, occurring due to the emergence of pathogenic variants in genes encoding elements of the epigenetic machinery, leads to the development of chromatinopathies. This group of hereditary diseases
includes 179 syndromes, some of which have overlapping phenotypes. Despite the fact that there is a variety of approaches to molecular diagnostics of chromatinopathies, it is not always possible to confirm the clinical diagnosis by traditional methods, thus the problem of optimizing diagnostic algorithms remains relevant. This article aims to represent an original approach to indirect diagnostics of chromatinopathies using the example of Rubinstein-Taybi syndrome, which is based on analyzing the methylation level of limited
regions of the genome. The study encompasses two methods of targeted quantitative analysis of DNA methylation, which are relatively accessible and can be integrated into diagnostic practice.

Background. Data on the genetic load of orphan hereditary diseases (OHDs) in human populations are few, variable across populations and ethnic groups, and on average account for 0.5-2% of the population. The results of a comprehensive genetic epidemiologic study of the population of the Republic of North Ossetia  Alania (RNOA) are presented.

Methods. The study was conducted in eight rural districts and the city of Vladikavkaz, with a total population of 543,817 people. The population was examined in accordance with the protocol of genetic epidemiologic studies developed in RCMG. 11199 patients with congenital and presumptive OHDs were examined. The diagnosis of OHDs was made in 2115 patients from 1489 families. The genetic load (per 1000 people) of AD, AR, and X-linked diseases in urban and rural populations was estimated. Rates of genetic load values between populations were compared using the χ2 method. Pearson correlation analysis between genetic load values and measures of genetic structure was performed in Statistica v. 23.

Results. The genetic load of AD, AR, and X-linked pathology in rural populations (3.21; 2.45; 0.99, respectively) was almost twice as high as in urban populations (1.42; 1.52; 0.81). Variability in the magnitude of genetic load between populations was revealed. The maximum genetic load values were registered in Irafsky district (4.94 in the district center, 11.72 in the rural population), and the minimum in Vladikavkaz (2.69/1000). To explain the heterogeneity of the OHDs load, a correlation between the OHDs load and the genetic structure of 17 populations was carried out, which showed the leading role of genetic drift in the revealed differentiation. Significant coefficients >0.80 were obtained in all cases.

Conclusions. The obtained values of AD, AR and X-linked disease genetic load in RNOA populations are characterized by variability with a large range of values (2.96-11.72/1000). Such variability is characteristic of populations of small ethnic groups: in Karachay-Cherkessia (4.76-11.82/1000), in Tatarstan (5.20-11.70/1000), in Bashkortostan (3.83-9.08/1000) and others. In the regions with Russian population there is also a variation of the OHDs genetic load, but the absolute values are lower.

 Duchenne muscular dystrophy is the most common muscular dystrophy among children. Mostly the cause of the disease is frame-shift deletions of exons 43-55 of the DMD gene, leading to the absence of expression of the functional dystrophin. The most optimal approach
to restoring the reading frame is skipping an additional exon. In order to completely remove an exon, it is necessary to introduce two double-stranded DNA breaks, which is associated with a number of negative consequences. However, permanent exon skipping can
also be achieved by disruption the splice site by a single DNA break with following repair by non-homologous end joining. To assess the feasibility of this strategy, we performe a bioinformatics and experimental screening of sgRNAs targeting the splice sites of exons
43-55. As a result, the most promising sites for editing were the acceptor splice sites of exons 54-55 and the donor splice sites of exons 43 and 53. In addition, we demonstrate the efficiency of Cas9 with the non-classical PAM sequence NGA. 

Background. Anovulation is a common cause of female infertility. Signal transduction by follicle-stimulating and luteinizing hormones receptors is substantial for the successful reproduction.

Aim: to study the contribution of intergenic interactions of FSHR rs6166 and LHCGR rs2293275 candidate gene variants to the development of anovulation.

Methods. The present study included 208 women from infertile couples who underwent assisted reproductive technologies, including women with anovulation and normally ovulating women with tubal and/or male factor. Women with reduced FSH and/or AMH serum levels were excluded from the study.

Results. The genotypes frequency distribution for FSHR rs6166 and LHCGR rs2293275 gene variants was AA (40%), AG (43%), GG (17%), and AA (9%), AG (52%), GG (39%), respectively. The present study revealed the two-locus FSHR rs6166 AG / LHCGR rs2293275 GG combination associated with the increased risk of anovulation (OR (95% CI) = 2.43 (1.48-4.01), p<0.001) In addition, among women carried genotype LHCGR rs2293275 AA, none experienced anovulation. The present study also revealed differences among women carrying the risk genotype. Anovulatory women with rs6166 AG / rs2293275 GG combined genotype had an increased AMH level, AFC and LH/FSH ratio and a decreased FSH level, compared to normally ovulating women with the same genotype of risk.

Conclusion. Present study proposes that FSHR rs6166 and LHCGR rs2293275 variants are good candidate markers for association studies, and together may provide an effective model for predicting the risk of anovulation.

Background. Constitutional trisomy 8 is a rare chromosomal abnormality in man. The exact incidence of trisomy 8 in live births remains unknown. Trisomy 8 is defined as the presence of three copies of chromosome 8 in every cell of an individual’s body—a condition that is usually causes the embryo death and is often detected in human spontaneous abortions. In instances of live births, trisomy 8 is predominantly associated with somatic mosaicism, with an estimated prevalence of 1:25 000 to 1:50,000, whose clinical presentation has a wide phenotypic variability Two cases are presented, demonstrating the tissue specificity of somatic mosaicism in constitutional trisomy 8, both in the presence and absence of clinically significant phenotypic abnormalities.

Aim: to assess the distribution and level of somatic mosaicism in tissues of different embryonic origins in mosaic trisomy 8 in two patients with abnormal phenotype and without specific clinical features.

Methods: conventional cytogenetic study, fluorescence in situ hybridization (FISH).

Results. The level of the abnormal clone in mosaic constitutional trisomy 8, as well as its distribution across various tissues, exhibited notable differences in a patient presenting with phenotype abnormalities and intellectual disability compared to case lacking clinically significant phenotype anomalies. It was observed that variability in the level of somatic mosaicism within tissues derived from the same embryonic lineage exists. Considering the tissue-specific nature of somatic mosaicism associated with trisomy 8, it is essential to investigate tissues originating from different germ layers when an abnormal clone is identified in the cells of a particular tissue.

Trismus-pseudocamptodactyly syndrome (TPS, distal arthrogryposis type 7) is a rare disease with autosomal dominant inheritance from the group of distal arthrogryposis. The most characteristic clinical manifestations of TPS are trismus and limited extension in the interphalangeal joints of the hand during dorsiflexion of the wrist (pseudocamptodactyly). The cause of the disease is the pathogenic
variant c.2021G>A (p.Arg674Gln) in the MYH8 gene, which has been identified in all cases of the syndrome described in the scientific medical literature. This study presents a new case of TPS caused by the rare variant NM_002472.3 (MYH8): c.2020C>T (p.Arg674Trp, rs762523289).