Marfan syndrome is a hereditary connective tissue disorder characterized by marked pleiotropy and clinical variability. The main disease manifestations involve three systems: skeletal, ocular, and cardiovascular. The condition is caused by pathogenic variants in the FBN1 gene, which encodes fibrillin-1, a protein essential for the formation and maintenance of the extracellular matrix. This article describes a familial case (the proband and his father) with clinical manifestations of Marfan syndrome. Whole-genome sequencing of the proband and his father revealed a previously unreported variant, c.5782T>A, p.(Cys1928Ser), in the FBN1 gene. Thus, a molecular genetic diagnosis of Marfan syndrome was established by identifying this novel pathogenic variant.Conclusion. A confirmed diagnosis at both the clinical and molecular genetic levels in both patients determines the further therapeutic strategy and enables timely primary and secondary disease prevention within the family.

Синдром Марфана - наследственное заболевание соединительной ткани, характеризующееся ярко выраженным плейотропизмом и клинической вариабельностью. Основные проявления заболевания затрагивают три системы: скелетную, зрительную и сердечно-сосудистую. Причиной заболевания являются патогенетически значимые варианты гена, отвечающего за синтез белка фибриллин-1, который играет ключевую роль в формировании и поддержании структуры соединительной ткани (fibrillin-1 gene, FBN1). B данной статье мы описываем семейный случай (пробанд и его отец) с клиническими проявлениями синдрома Марфана. В результате секвенирования полного генома пробанда и отца был выявлен ранее не описанный вариант нуклеотидной последовательности с. 5782Т>А, р.(Cys1928Ser) в гене FBN1 в гетерозиготном состоянии. Таким образом, был установлен молекулярно-генетический диагноз синдром Марфана, путем обнаружения нового патогенного варианта в гене FBN1. Выводы. Постановка диагноза на клиническом и молекулярно-генетическом уровне у обоих пациентов определяет дальнейшую терапевтическую тактику и открывает возможности для своевременной первичной и вторичной профилактики заболевания в семье.

Palmoplantar keratoderma is a clinically polymorphic disease with heterogenous etiology characterized by pronounced hyperkeratotic changes on the surface of the palms and soles. Hereditary forms of palmoplantar keratoderma are predominantly described by various variants in genes belonging to keratin family with autosomal dominant inheritance. A familial case of palmoplantar keratoderma is described. The analysis of family tree suggested autosomal dominant inheritance. Clinical manifestations included hyperkeratosis, xeroderma especially on the skin of the palms and feet: skin thickening with peeling and cracks, smoothed skin pattern. A previously undescribed and probably pathogenic c.103T>G variant of the AQP5 gene in heterozygous state in the proband, her mother and maternal grandfather was revealed as a result of whole genome sequencing. The presented clinical case is of interest for dermatologists due to the occasional incidence of palmoplantar keratoderma caused by variants in the AQP5 gene in clinical practice. Thus, the following diagnosis was established depending on the anamnestic data, clinical picture and examination results in the family: Bothnian palmoplantar keratoderma caused by a probably pathogenic variant in the AQP5 gene.

Ладонно-подошвенная кератодермия - клинически полиморфное заболевание с гетерогенной этиологией, для которого характерны выраженные гиперкератотические изменения на поверхности ладоней и подошв. Наследственные формы ладонно-подошвенной кератодермии преимущественно описаны различными вариантами в генах, относящихся к семейству кератинов, с аутосомно-доминантным типом наследования. Представлено описание семейного случая ладонно-подошвенной кератодермии. Анализ семейной родословной предполагал аутосомно-доминантный тип наследования. Клинические проявления включали гиперкератоз, сухость кожных покровов, особенно кожи ладоней и стоп: утолщение кожи с шелушением и трещинами, сглаженный кожный рисунок. В результате полногеномного секвенирования выявлен ранее не описанный вероятно патогенный вариант c.103T>G гена AQP5 в гетерозиготном состоянии у пробанда, ее матери и деда по материнской линии. Приведенный клинический случай представляет интерес для дерматологов в связи с редкой встречаемостью в клинической практике ладонно-подошвенной кератодермии, обусловленной вариантами в гене AQP5. Таким образом, на основании данных анамнеза, клинической картины и результатов обследования в семье поставлен диагноз: ладонно-подошвенная кератодермия ботнического типа, обусловленная вероятно патогенным вариантом в гене AQP5.

Background. DNA methylation regulates numerous biological processes, mediating normal development. Alterations in methylation patterns are associated with multiple pathological conditions like hereditary diseases and cancer, making them valuable clinical biomarkers for patient stratification, disease monitoring, early diagnosis, and prediction of response to therapy. Highly targeted, high-throughput methodologies focusing on critical genomic loci enable precise identification of distinct methylation signatures. The aim of the study was to analyze and summarize literature data describing the use of high-throughput DNA methylation analysis technologies, including those based on targeted approaches. Material and Methods. A systematic analysis of literature data was conducted using the PubMed, Web of Science, and Scopus databases, focusing on the characteristics of high-throughput DNA methylation analysis used in cancer and some genetic diseases. A total of 113 sources were analyzed, chronologically covering the period from 2000 to June 2025, 32 of which were used to write the review.

Results. The existing technologies for high-throughput methylome analysis, DNA conversion methods, and their advantages and limitations were summarized. In addition, the current targeted enrichment methods, their strengths and weaknesses, and potential applications in scientific and diagnostic practice were discussed.

Conclusion. DNA methylation analysis has evolved from a basic research tool into a cornerstone of translational medicine, particularly in oncology. Modern methylome analysis techniques facilitate the discovery of epigenetic markers critical for diagnosing diseases, assessing prognosis, guiding therapy selection, and identifying molecular targets for targeted drugs. Targeted DNA enrichment increases analytical precision and sensitivity while reducing costs. Furthermore, specialized strategies permit targeted analysis even with challenging samples. Combined with the flexibility to focus on specific genomic regions, these advantages make targeted approaches viable not only in academic research but also in routine clinical diagnostics.

Using a specific case study on the classification of the Turkic languages of Southern Siberia, this paper examines the potential for combining data from linguistic and population genetic studies. Analysis of similar rules in several dialects belonging to three Turkic genealogical language groups suggests that the influence of these rules in each group is only partly related to a Sayan-Samoyedic substrate, most likely due to language shift that is, the transition of the Sayan Samoyedic people to several Turkic languages. A similar hypothesis was previously proposed by A. Dulzon (Andreas Dulson), but it has not been supported by comparative historical analysis. For Northern Altaic idioms, it appears more likely that the Sayan Samoyeds themselves did not transite to these lects, but rather that a secondary language shift occurred among the Shors, who were already Samoyeds at that time and had adopted a Turkic language. Population genetic data support this hypothesis.

Aim. To assess the relationship between the respiration of mitochondria of peripheral blood leukocytes and mitochondrial DNA (mtDNA) polymorphism in patients with coronary heart disease (CHD) depending on the risk of developing sudden cardiac death (SCD).Materials and methods. We formed two groups of patients: the main group - patients with CHD and the high risk of SCD (n = 107); the comparison group - patients with stable course of CHD without the risk of SCD (n = 50). Using methods of high-throughput sequencing, we determined patients’ haplogroup and carriage of mtDNA polymorphisms A2706G, G3010A and G9055A. The respiratory activity of isolated mitochondria from peripheral blood leukocytes was assessed by amperometric method using NADand FAD-dependent oxidation substrates.Results. In both studied groups, H, U, and J haplogroups were predominant (74.5% and 92.5%, respectively, for the main group and the comparison group). There were more minor haplogroups in the main group than in the comparison group. The frequencies of occurrence of polymorphisms A2706G, G3010A, and G9055A did not significantly differ between the groups. In the main group, carriage of the A2706G polymorphism was associated with a decrease in the respiratory control ratio (RC) in FAD-dependent respiration (p = 0.05), and in the comparison group it was associated with a decrease in oxygen consumption rate (OCR) in the V4 metabolic state in both NADand FAD-dependent respiration (p = 0.002 and p = 0.008, respectively) without changing in RC. In the main group, carriage of the G9055A polymorphism was associated with a decrease in OCR in the V3 metabolic state (p = 0.037) in FAD-dependent respiration. For the G3010A polymorphism, no association with mitochondrial respiration was found in the studied groups.Conclusion. In patients with CHD, regardless of the risk of SCD, the frequencies of haplogroups H, U, and J and mtDNA polymorphisms A2706G, G3010A, and G9055A do not differ significantly. In patients with high risk of SCD, carriage of the A2706G polymorphism is associated with a decrease in RC in FAD-dependent respiration, and the G9055A polymorphism is associated with a decrease in OCR in V3 during FAD-dependent respiration.

Introduction . Aortic arch anomalies, especially the “bovine arch”, can cause the development of an ascending aortic aneurysm. There is a high coefficient of heritability of this pathology, however, genetic studies are rare. Since the “bovine arch” is one of the variants of the development of the aortic arch and large vessels during embryogenesis, this pathology may be associated with genes encoding proteins involved in the embryonic development of the cardiovascular system. Aim: To identify rare, clinically significant variants of genes of cardiovascular embryonic development in patients with sporadic ascending aortic aneurysm and a “bovine arch”. Material and Methods . The study included 42 patients with a sporadic form of ascending aortic aneurysm, including 11 patients with a “bovine arch”. Analysis of the clinical exome was performed based on DNA sequencing data using Clinical Exome Solution (Sophia Genetics, Switzerland) and NextSeq 500 genetic sequencer (Illumina, USA). The search for rare, clinically significant variants (minor allele frequency <1%) was carried out in exons and adjacent introns of 120 genes of embryonic development of the cardiovascular system. Validation of identified variants was performed using Sanger sequencing. Results. In patients with aortic aneurysm and “bovine arch”, the following clinically significant variants were identified: the pathogenic variant c.610-2A>G of the CCDC39 gene, which is a single-nucleotide substitution leading to the loss of the acceptor splice site (ΔScore = 0.97 Spliceailookup) and a variant of uncertain clinical significance (VUS) c.2564T>C in the ANKS6 gene, which has high pathogenicity rates on the CADD (Phred = 28.3) and AlphaMissense (0.972) scales. A likely pathogenic variant c.1151T>C of the ACVR2B gene was identified in the group of patients with aortic aneurysm without supraaortic vessels anomaly (AlphaMissense = 0.966). Among the 38 genes whose sequences revealed VUS in both groups of patients, the protein products of 17 (44.7%) are involved in the functioning of cilia and microtubules, and the proteins encoded by the genes MKS1, CCDC40, DNAAF1, ANKS6, CCDC39, DNAH5, DNAAF3 are also responsible for the development of the cardiovascular system. Conclusion . Rare, clinically significant variants in the CCDC39 and ANKS6 genes, which are crucial for primary cilia function, contribute to the development of sporadic ascending aortic aneurysm in combination with a “bull’s arch.” When a normal aortic arch is present, variants in the ACVR2B gene, belonging to the TGF-beta signaling protein superfamily, play an important role.

Background. Fetal growth retardation (FGR) remains one of the leading causes of perinatal morbidity and a major risk factor for longterm adverse health outcomes in children, including an increased likelihood of neurological, metabolic, and cardiovascular disorders. Despite extensive research interest, the molecular mechanisms underlying FGR are still insufficiently understood. In particular, little is known about the role of post-transcriptional regulation in the development of this condition. Alternative splicing is of special interest. It determines transcriptome diversity and expands the functional capacities of cells. Through this mechanism, cells gain the ability to adapt to pathological stimuli. At the same time, it influences their susceptibility to disease, including obstetric complications. Aim : To characterize alternative splicing profiles in placental decidual cells (DCs) that determine the severity of fetal growth retardation. Material and Methods. The study was conducted on placental tissue samples from patients with moderate and severe forms of FGR. Whole-transcriptome analysis was performed on decidual cells isolated by laser microdissection from stained thin tissue sections. Whole-genome ribonucleic acid (RNA) sequencing was performed using the SMARTer Stranded Total RNA-Seq kit v2 (Takara BIO). Alternative splicing events were analyzed with the MAJIQ package under a Linux operating system. Results. In the analyzed samples, 13,688 alternative splicing (AS) events were detected across 4,002 genes expressed in decidual cells. More than 52% of these events were identical between both groups. In severe FGR, both annotated and de novo events demonstrated a statistically significant decrease in the frequency of the alternative first exon (χ2 = 8.48, p = 0.004; χ2 = 6.15, p = 0.014, respectively). The alternatively spliced genes specific to severe FGR were involved in the following biological processes: catalytic activity acting on nucleic acids (pFDR = 0.020), regulation of GTPase activity (pFDR = 0.021), regulation of nucleoside triphosphatase activity (pFDR = 0.021), and peptide N-acetyltransferase activity (pFDR = 0.028). Comparison of the moderate and severe FGR groups identified 84 differentially spliced genes (0.200 < deltaPSI < 0.648; p < 0.05). These genes were significantly associated with biological and signaling pathways including multiple types of DNA repair, the ligand-gated ion channel pathway, vesicular transport to the plasma membrane, regulation of mRNA metabolism, peroxisome organization, lysosome organization, morphogenesis, the SMAD signaling pathway, sulfur metabolism, and ATP-dependent chromatin remodeling. Conclusion . The data indicate a specific set of AS-related molecular changes characteristic of FGR, regardless of its severity. AS patterns unique to severe FGR are associated with disruptions of fundamental cellular regulatory systems. Functional annotation of differentially spliced genes suggests that AS affects post-transcriptional control, cellular architecture, and intercellular signaling interactions in severe FGR.

The article discusses the relationship between modern human population genetics, medical genetics, and personalized and evolutionary medicine. It is shown that population genomics data are one of the foundations for the development and implementation of personalized approaches in medicine. The importance of evolutionary medicine as a developing area of modern biomedicine aimed at studying human diseases and health in an evolutionary context is demonstrated.

The main results of the Scientific and Technical Program of the Union State “DNA Identification” and implementation of reagent kits and technologies developed under the Program to establish the ethnogeographical and population origin of an unknown individual on the basis of his DNA are presented. The developed reagent kits are designed for DNA identification and are adapted to existing national reagents and their instrumentation used in Union State forensic laboratories.

Objective. To study the clinical and anamnestic features in patients with various forms of fetal stunting to determine the risk factors for the development of this pregnancy complication. Material and methods. The study included 329 patients, who, depending on pregnancy outcomes, were divided into 3 groups: The 1st group (main group) included 165 women whose pregnancy was complicated by insufficient fetal growth (IFG). The main group was divided into 2 subgroups: 1a — 72 patients, whose pregnancy was complicated by the development of a fetus of low gestational age (LGA), 1b — 93 patients, whose pregnancy was complicated by fetal growth retardation. The 2nd group (comparison) included 164 patients whose pregnancy ended with the birth of a live full-term baby without signs of insufficient growth. The somatic and obstetric anamnesis and the course of pregnancy were studied in all patients. Results. It was shown that patients younger than 20 years of age were more likely to occur in the SGA and FGR subgroups (odds ratio — OR 5.8; 95% confidence interval — CI 1.450—23.039; p=0.010 and OR 4.4; 95% CI 1.102—17.322; p=0.039, respectively). An analysis of the maternal history showed that preterm birth was more common in the SGA group than in the comparison group (OR 2.8; 95% CI 1.077—7.165; p=0.038). Insufficient fetal growth in the previous pregnancy was more common in women of the main group and increased the chance of this pregnancy complication in the present pregnancy: 4.3 times (OR 4.3; 95% CI 1.282—14.330; p=0.016) for FGR and 3.7 times (OR 3.7; 95% CI 0.994—13.306; p=0.072) for a fetus of low weight for this gestational age. Uterine scarring was more common in patients of the SGA group than in the comparison group (OR 2.4; 95% CI 1.143—4.867; p=0.029). Early toxicosis and gestational diabetes mellitus were more common in patients in the FGR group than in the comparison group (OR 3.1; 95% CI 1.622—6.011; p<0.001 and OR 2.1; 95% CI 1.181—3.829; p=0.014). Conclusion. The study identified new risk factors for breast undergrowth. It is necessary to take into account the patient’s age, the presence of a scar on the uterus, premature birth, insufficient fetal growth in a previous pregnancy, early toxicosis, and gestational diabetes mellitus in order to timely assess the risk of insufficient fetal growth.

Aim. To evaluate the role of biochemical and biophysical parameters in the combined first-trimester prenatal screening for the development of clinical forms of fetal growth insufficiency. Materials and methods . Group I (main) included 73 patients, whose pregnancies were complicated by the fetal growth insufficiency. The main group was divided into two subgroups: Ia with 30 patients whose pregnancies were complicated by fetal growth restriction (FGR) and Ib with 43 patients whose pregnancies were complicated by small for gestational age fetuses (SGA). Group II (control) included 118 patients whose pregnancies resulted in the birth of a live, full-term infant with normal height and weight. All patients underwent combined first-trimester prenatal screening with calculation of biochemical (pregnancy-associated plasma protein A (PAPP-A), free β-subunit of human chorionic gonadotropin (β-hCG) and biophysical (mean arterial pressure (MAP), uterine artery pulsatility index (PI) parameters, the values of which were subsequently analyzed. Results. The level of PAPP-A was statistically significantly lower in the FGR group (0.793 MoM) compared to the control group (1.048 MoM), p = 0.005. The level of PAPP-A in the blood below 0.793 MoM increases the risk of fetal growth restriction by 3.244 times (odds ratio (OR) = 3.244; 95% confidence interval (95% CI) 1.394–7.554, p = 0.005). An increase in the pulsation index was found in Doppler ultrasound of the uterine arteries in patients with FGR compared to the SGA group (OR = 2.254; 95% CI 0.990–5.129, p = 0.017). Statistically significant differences were not found in the studied parameters of the combined first-trimester prenatal screening in relation to the development of SGA. Conclusion. Differences in the biochemical and biophysical parameters of combined prenatal screening for the clinical forms of the fetal growth insufficiency were identified. Further research is needed to identify new prognostic markers of fetal growth insufficiency, which will help reduce perinatal losses. Additional research is required to expand the sample size of the Russian population to clarify the role of the prenatal screening components.

Fluorescent in situ hybridization (FISH) remains an indispensable tool for molecular diagnostics, which makes it possible to detect chromosomal abnormalities underlying many hereditary and oncological diseases with high accuracy. The advancement of medicine towards personalized approaches and the expansion of the spectrum of diagnosed pathologies require constant improvement of methods for synthesizing DNA probes. Despite existing limitations such as the cost and complexity of synthesis, the future of FISH diagnostics is linked to the development of highly specific, multiplex, and affordable probes that will enable the transition to complex genome and transcriptome analysis. The aim of this article was to reflect the evolution of probe production methods from classical to high-tech, including SABER-FISH, CRISPR/Cas9 (CASFISH), and smFISH technologies.