Wolf-Hirschhorn syndrome is caused by partial loss of material from the distal portion of the short arm of chromosome 4 (4p16.3), and is considered a contiguous gene syndrome. The craniofacial view of patients includes the «Greek warrior helmet» appeara nce of the nose, high forehead, prominent glabella, hypertelorism, highly arched eyebrows, protruding eyes, epican thal folds, short philtrum, distinct mouth with down-turned corners, micrognathia. This syndrome is characterized by pre- and postnatal delay in anthropometric parameters, congenital malformations of various systems, mental retardation and a seizure disorder.

   The purpose of this review is to provide detailed data on the etiology, pathogenesis, clinical presentation of the syndrome, as well as the possibilities of medical care for patients.

   The current review highlights important medical aspects: nutritional problems, the nature of epileptic seizures and the possibilities of therapy, psychiatric care, features of anesthesia.

   The purpose of this research was to develop amino acid and acylcarnitine reference intervals in neonates of different gestational ages and birth weight.

   Concentrations of 11 amino acids, 31 acylcarnitines and succinylacetone were measured by tandem mass spectrometry (MS/MS) in neonates born in Moscow between 2021 and 2022. The analysis of the amino acids and acylcarnitines spectra was performed on the 4^th day of life in neonates born after 37 weeks’ gestation and on days 7 and 14 in neonates born before 37 weeks’ gestation. All neonates were divided into 5 groups, depending on the gestational age at the time of birth and on the birth weights. The 0.5^th -99.5^th percentiles for each biomarker were compared to assess the significance of the obtained results and thus to develop reference intervals. 226225 neonate blood samples were analyzed. When assessing the difference in the amino acid and acylcarnitine profiles between different groups of neonates, the most significant differences were discovered in the concentration of arginine, leucine, methionine, phenylalanine, tyrosine, valine and proline. The concentration of these amino acids was significantly higher in the groups with low body weight and shorter gestational age at birth. When comparing the concentrations of acylcarnitines, an increase in the concentrations of C0, C4, C5, C6, C8 and C10 was highlighted in the newborns with a shorter gestational age and lower birth weight in comparison to the term neonates. Thus, this research demonstrated the complexity of interpreting the TMS data obtained from preterm neonates as well as the need in consideration of the gestational age in the analysis of neonatal screening. The research highlighted the importance of reference intervals for neonates born before 37 weeks’ gestation.

   Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, accounting for approximately one-third of hospitalizations for heart rhythm disorders. AF is associated with an increased risk of death, stroke and other thrombotic complications, impaired quality of life, decreased exercise tolerance, and left ventricular dysfunction. Laboratory diagnosis of predisposition to the occurrence of thrombotic complications is carried out by determining the polymorphism of genes of hemostasis factors. Of particular interest is the identification of cases of congenital thrombophilia resulting from molecular defects in the hemostasis system or its inhibition processes. The study included 41 healthy volunteers and 52 patients with AF: paroxysmal and persistent forms. Of these, 8 patients (15.38 %) developed thrombotic complications against the background of adequate anticoagulant therapy. Genetic methods of investigation included DNA isolation and examination of polymorphic variants of genes of the hemostasis system and platelet receptors using real-time polymerase chain reaction method. Genotype frequencies were compared using Pearson’s χ² criterion with Yates correction (Y). The nature of associations of genotypes with thrombotic complications was assessed using odds ratios (OR) and their 95% confidence interval (95 % CI). Comparative analysis of hemostasis system factors genotypes: rs1799963 FII, rs6025 FV, rs1800790 FGB, rs1799899 PAI-1 and platelet receptors: rs1126643 ITGA2, rs5918 ITGB3 in patients with atrial fibrillation and controls showed no significant differences. The studied genetic polymorphisms of hemostasis system factors and platelet receptors were not associated with the risk of thrombotic complications in patients with atrial fibrillation.

   Three clinical cases of children with achondroplasia before the age of 1 year were analysed to determine the causes of respiratory failure (DN). It was found that despite a single molecularly genetically confirmed pathology, achondroplasia, the triggers of severe DN, leading to death in two cases and to ventilatory dependence in one, were different in three children of the first year of life. The presence of a single background mechanism of respiratory distress (caudal CMN group compression syndrome) suggests the development of a special algorithm for the management of children with AHP from the first days of life, given the high risk of respiratory distress, provoked by various triggers, of severe severity, leading to irreversible consequences.

   Wolf–Hirshhorn syndrome is one of the rare but recognizable hereditary syndromes, of which several dozen clinical cases have been described. The article describes three clinical observations of children with Wolff-Hirschhorn syndrome. In two children, the diagnosis was confirmed by high-resolution chromosomal microarray analysis, in one by standard cytogenetic examination. In two cases, the chromosomal imbalance arose de novo. Two children had an isolated 4p deletion (p15.3 and 4p16.3), one had a combination with an 8p23.1-p23.3 microduplication. All patients had common phenotypic features: orbital hypertelorism, dysplastic low-lying auricles, short filter small upper lip. All children had pronounced muscular hypotonia from birth, psychomotor retardation and convulsive syndrome with the need for prescription and individual selection of anticonvulsant therapy. All children were diagnosed with severe protein-energy deficiency, which is difficult to correct due to poor tolerance of artificial mixtures. One patient was diagnosed with enchondroma. Our experience presented in this article allows us to supplement the data on the syndrome and expand the cohort of cases described in the literature.

   Expression of miR-100 is increased in unstable carotid atherosclerotic plaques. It can be associated with CpG sites methylation variability in the MIR100 gene region and its adjacent regulatory regions.

   The aim of our work was to analyze the association of DNA methylation level in the putative regulatory region of MIR100 gene with advanced carotid atherosclerosis using targeted bisulfite sequencing.

   We analyzed DNA samples of paired vessel tissues and blood leukocytes of patients with advanced atherosclerosis of the carotid arteries (n = 19), as well as blood leukocytes of healthy individuals (n = 18). As a result, we revealed tissue-specific methylation pattern of the chr11:122,024,891-122,025,506 region (GRCh37/hg19 genome assembly) including E-box (see Chen D. et al, 2014 for more information). The methylation level in unaffected carotid arteries was decreased compared to both veins (p < 0.001) and peripheral blood leukocytes (p < 0.007). Significant hypomethylation was observed in atherosclerotic carotid plaques relative to unaffected carotid arteries, but the level of DNA methylation in blood leukocytes of patients with atherosclerosis did not differ from that in blood leukocytes of the control group. Our findings suggest tissue-specific methylation of the putative regulatory region of MIR100 gene (E-box) and its possible association to atherosclerosis. Nevertheless, the methylation of the chr11:122,024,891-122,025,506 region cannot be used as a diagnostic biomarker of atherosclerosis.

   We performed a whole-genome comparative analysis of gene expression in tissues of patients with carotid artery atherosclerosis using HumanHT-12_V4 BeadChip (Illumina, USA) microarray. We compared the expression between cells of the carotid artery in the area of atherosclerotic plaques (CAP, n = 3) and intact internal mammary arteries (IMA, n = 2). The targeted expression assessment was performed for ADAMDEC1, ITGB5, TIMP2, and ММР3 genes in blood leukocytes of patients (n = 21). A significant increase in expression of extracellular matrix organization genes (CD44, COL1A2, COL3A1, COL5A2, FMOD, HAPLN1, ITGA11, ITGAV, SPARC, SPP1, SULF1, TIMP1; |FC|≥2; pFDR = 1,44×10-7) was detected in CAP. The ADAMDEC1, ITGB5, and TIMP2 genes, are characterized by increased expression in CAP, compared with IMA (рFDR=0.018; рFDR = 0.011; рFDR=0.006, respectively). The ADAMDEC1, ITGB5, and TIMP2 genes are also expressed in peripheral blood leukocytes of patients; the highest level of expression is shown for the TIMP2 gene. Assessment of the expression level changes depending on genotypes showed that carriers of the TT genotype of rs1007856 in the ITGB5 gene have the lowest level of gene expression compared to carriers of the CC and CT genotypes (p = 0.034). Thus, carotid atherosclerosis is associated with an increase in the functional activity of fibrogenesis genes in vessels and blood leukocytes. The rs1007856 polymorphism is an eQTL for the ITGB5 gene in patients’ blood leukocytes.