Copy number variations (CNV) in the STRC gene are the main cause of autosomal recessive deafness type 16 (DFNB16, OMIM #603720). Genetic testing of DFNB16 is complicated by the complexity of the chromosomal region (15q15.3) containing a segmental duplication of five genes, including the STRC gene and its highly homologous pseudogene STRCP1. Clinically, DFNB16 is associated with a mild and moderate form of hearing loss, which, in our opinion, is due to the compensatory effect of the pseudogene, as was shown in spinal muscular atrophy. In this regard, to understand the molecular mechanisms of occurrence and clinical features of DFNB16, it is relevant to study the number of copies of not only the STRC gene, but also the STRCP1 pseudogene. In total, copy number changes in the STRC gene were detected in 7 (6.2%) individuals, and in the STRCP1 pseudogene in 16 (14.1%) individuals. It was found that these copy number changes most likely occurred as a result of unequal crossing over (STRC/STRCP1 – deletion/deletion or norm), cases associated with gene conversion (STRC/STRCP1 – deletion/duplication or vice versa duplication/deletion) were not detected. Comparative analysis of the frequency of altered copies of the STRC gene and the STRCP1 pseudogene revealed reliable differences between deletions (1.8%) and duplications (11.5%) in the STRCP1 pseudogene region (χ²=8.64, p<0.01), while in the STRC gene region, such differences were not observed (deletions – 2.6%, duplications – 3.5%, χ²=0.15, p>0.05). A decrease in the frequency of extended deletions in the STRCP1 pseudogene region in the Yakut population is probably associated with selection pressure, which indicates a possible compensatory role of the pseudogene in the absence of a functional copy of STRC.

Introduction. Approximately one-third of all pregnancies end in early miscarriage. The highest risk period for spontaneous pregnancy loss occurs within the first 12 weeks, during which 80% of all spontaneous abortions take place. Cell adhesion molecules are key components throughout the reproductive cycle and may influence the risk of pregnancy loss.

Objective: to study the influence of gene polymorphisms CDH1 (rs16260, rs5030625), SELL (rs2229569, rs1131498), ITGB3 (rs5918), ITGA2 (rs1126643) on the risk of pregnancy loss in the first trimester in women from the Rostov region.

Methods. DNA was extracted from peripheral blood cells using a thermocoagulation method. Single nucleotide polymorphisms were analyzed by allele-specific PCR and restriction fragment length polymorphism analysis.

Results. No statistically significant differences were found in the distribution of genotypes and alleles of the studied single nucleotide polymorphisms between women with normal pregnancies and those with first-trimester pregnancy loss. In the present study, there were no statistically significant differences in the distribution of genotypes and alleles for the studied single nucleotide substitutions between women with normal pregnancy and women with miscarriage in the first trimester. However, it has been established that there is a synergy between polymorphic loci of the CDH1, SELL and ITGA2 genes.

PROS (PIK3CA-Related Overgrowth Spectrum) is a tissue overgrowth syndrome associated with mutations in the PIK3CA gene. As approaches to pathogenetic treatment with PIK3-associated signaling pathway inhibitors (sirolimus, alpelisib, miransertib) are being developed, the demand for molecular genetic testing of patients with suspected PROS has arisen. 53 patients with tissue overgrowth affecting upper or lower extremities were observed in St.-Petersburg State Pediatric University Clinic in 2018-2023 yrs. Patients had molecular genetic testing using digital droplet PCR and targeted high-throughput sequencing. Pathogenic PIK3CA variants were identified in 17 cases. In the isolated form of the disease mutations were detected much more rarely in comparison with the syndromal form of this pathology (8 / 39 (21%) vs. 9 / 14 (64%), p = 0.006).

Background. Adverse childhood experiences (ACEs) are known to increase the risk of schizophrenia. One putative mechanism of the ACEs’ influence on the disease is an increased activation of the immune system. Thus, genetic polymorphism of the immune system may cause variability in disease manifestations, including cognitive deficits, which is important to consider in the prevention and treatment of psychosis.

Aim: to assess the effect of genetically determined characteristics of interleukin production on the relations between ACEs and cognitive deficit in patients.

Methods. The sample included 203 schizophrenia patients aged 16–45 years who completed tests of verbal fluency (VF) and attention/ working memory. The presence of ACEs, polygenic risk scores (PRS) of the concentration of proinflammatory interleukins (IL-6, IL-8, IL-18, IL-27) and a multigenic risk score (MGS) of the deleteriousness impact of mutations in the genes of regulatory interleukins (IL-2, IL-4, IL-10, IL-13) were assessed for each participant. The moderation effect of genetic variables on the association between ACEs and cognition was evaluated with covariance analysis, controlling for sex, schizophrenia PRS, intelligence PRS, and two ancestry-related principal components.

Results. The IL6-PRS was a moderator of the association between ACEs and VF. The unfavorable influence of high IL6-PRS on VF took place in women with ACEs. IL8-PRS and MGS associated with cognition regardless of ACEs.

Conclusion. The results confirm the hypothesis of a negative effect of genetic polymorphism leading to an increase in IL-6 concentration on the cognitive functions of schizophrenia patients with ACEs and indicate that the effect is sex-specific.

Introduction. The absence of pathognomonic symptoms and effective early screening methods of ovarian cancer dictates the need for search new molecular genetic markers of this disease.

Aim: to find the polymorphic variant rs113488022/BRAF in women from the Republic of Bashkortostan.

Methods. This study included DNA samples from women with sporadic ovarian cancer (n=210), hereditary ovarian cancer (n=72), and women without oncopathology (n=208). Genotyping was performed using real-time PCR.

Results. No carriers of the minor allele of the polymorphic locus rs113488022 of the BRAF gene were identified among the women included in the study.

Conclusions. The absence of carriers of the rare allele rs113488022/BRAF may be explained by the low prevalence of this polymorphism in the region, highlighting the need for further genetic research to identify other potential genetic predictors of ovarian cancer.

The analysis of genotoxic effect of potential mutagens in humans usually is carried out in chronic exposure industrial conditions, data on genotoxic effect of acute poisoning are practically absent, therefore the examination of really affected people is of special interest. The aim of the study is to investigate the level of chromosomal aberrations in the acute poisoned with nitrogen oxides workers of the rocket and space industry. The results of cytogenetic examination of 18 persons with nitrogen oxides acute inhalation poisoning during routine cleaning of a railroad tank car from amyl are presented. An increased level of unstable chromosomal aberrations was found, mainly due to a statistically significant increase in the frequency of chromatid-type aberrations. which are typical for chemical mutagenesis. These changes were detected after normalization of other laboratory parameters and clinical recovery of the victims. Thus, nonspecific chromosomal damages typical occur as a result of nitrogen oxides acute poisoning.

Netherton syndrome (OMIM #256500) is a rare autosomal recessive syndrome, characterized by erythroderma, parakeratosis, trichorrhexis invaginate, also known like «bamboo hairs», immunodefciciency, atopic manifestations and hypereosinophilia. Correlations between genotype and phenotype have been observed in patients with Netherton syndrome: variants located closer to the 5′-untranslated region of the gene are associated with more severe phenotypes, while variants closer to the 3′-end of the gene are linked to milder phenotype. No patients with biallelic variants in exons 29-33 have been described in the literature, suggesting a possible unknown compensatory mechanism. This study presents a case of a patient with dermatological and immunological manifestations, harboring a previously unreported homozygous variant in exon 23 of the SPINK5 gene, which may be associated with a relatively mild disease. This clinical case underscores the need for a multidisciplinary approach in managing Netherton syndrome patients and the need for further studiesto better understand the pathogenesis of the disease and explore potential therapeutic strategies.

Identification of pathogenic genome variants not associated with the referral diagnosis for DNA diagnostics (secondary findings, SFs) allows diagnosing monogenic diseases before they manifest and starting preventive treatment in such patients. The aim of this study was to assess the occurrence of pathogenic variants in clinically significant genes recommended for testing by international guidelines in a cohort of individuals from the NMRC TPM biobank. The study included 4170 persons who underwent DNA diagnostics of hereditary diseases at the NMRC TPM. DNA sequencing was performed on the Illumina platform. 86 SFs were identified in 26 recommended genes in 126 (3%) patients. The procedure for reporting SFs to the carriers and further tactics for managing such patients are currently being developed.

Breast cancer (BC) ranks first in the world among oncological disorders in women. Aim of the study – to perform analysis of contribution of catalase gene polymorphic variant CAT-21 A>T rs7943316 and DNA repair genes: XPD 2251 T>G rs13181, ADPRT 2285 T>C rs11610, hOGG1 977 C>G rs1052133 in breast cancer risk development in women. 298 samples of peripheral blood were collected from women with breast cancer and 287 samples as controls were used. Analysis showed significance of combinations of CAT-21 A>T rs7943316 and XPD 2251 T>G rs13181 genotypes: OR-3.02(1.15-7.92). It was demonstrated ability for formation of breast cancer risk via combination of certain genotypes of antioxidant and DNA repair genes.

Lung cancer (LC) is the leading cause of cancer incidence and mortality worldwide. Small cell LC (SCLC) is an aggressive subtype of LC that is initially sensitive to chemotherapy but subsequently becomes chemo-refractory. The aim of the study was to evaluate the frequency of mutations in EGFR, PIK3CA, BRAF, and KRAS genes associated with response to targeted drugs in SCLC patients. The study was performed using real-time PCR. The frequencies of mutations in PIK3CA and KRAS genes in SCLC patients were 5.63% and 1.41%, respectively; no mutations were found in BRAF and EGFR genes. One case of combined carriage of the H1047X mutation in PIK3CA gene and Q61K mutation in KRAS gene was identified.

A clinical case of a combination of phenotypic manifestations of Angelman and Rett syndromes in a patient with delayed motor development, intellectual disability, neurological manifestations and behavioral characteristics are presented. Genomic changes in the Xq28 locus were identified using the method of chromosomal microarray analysis. Based on the obtained results and literature data, a variant of the formation of genotype-phenotype associations is discussed.

The study presents the frequency analysis of different genetic types of MED in a cohort of 99 unrelated patients from the Russian population. The most prevalent types were MED type 4 (64,6%) and MED type 1 (20,2%). The rare MED types 2, 3, and 5 represented 15,2% of cases. A total of 45 nucleotide variants were identified in the SLC26A2, COMP, COL9A2, COL9A3, and MATN3 genes, with 26 being novel (57,7%). The findings highlight that the broad use of massively parallel sequencing significantly improves the identification of different genetic types of MED.

Studies have shown that the level of vitamin D and polymorphisms in the genes of the vitamin D system are factors associated with susceptibility to the development of multiple sclerosis. The purpose of this work was to investigate the frequency of six SNPs in the genes of the vitamin D system – VDR and GC – in patients with multiple sclerosis (MS, n=145) and in a population control group (CG, n=96). DNA, extracted from blood samples, was genotyped using real-time PCR. The frequency and spectrum of the investigated SNP combinations are discussed. The study identified 22 variant combinations of SNPs in the population control group and 15 variants in the MS patient group. The most common variant among MS patients was GCCCGC. Two variants were identified that occurred with varying frequencies – GCCCGA and GCCCAC. The results obtained support the data on the correlation of vitamin D system genes with the development of MS.

Osteogenesis imperfecta type I is an autosomal dominant generalized connective tissue disorder predominantly characterized by bone fragility. We describe a familial case of osteogenesis imperfecta type I caused by a novel splice site variant c.2028+1G>A of the COL1A1 1gene.

Introduction. Polygenic risk score (PRS) development allow to evaluate polygenic contribution to the phenotype, particularly, to blood lipid levels. However, PRS applicability to the Russian population was rarely estimated.

Aim. To evaluate the applicability of already existent PRS and to develop own PRS for blood lipid levels for the Russian population; to study the possibility of PRS application for differential diagnostics.

Methods. Populational samples from Ivanovo (n=1673) and Vologda (n=817) regions from the ESSE-RF study, sample of patients with linical diagnosis familial hypercholesterolemia (FH) (n=353) and prominent hypertriglyceridemia (HTG) (n=148) were used in the study.

Results. Coefficient of determination was shown to increase by 2-4% when developing own PRS compared to existing ones, depending on the phenotype studied. Such PRS can be applied for differential diagnostics of patients with familial FH and HTG in the population.

Conclusions. Blood lipid PRS are applicable for the inhabitants of the European part of Russia. Such PRS can be used for differential diagnostics.

Since January 2023, in the Russian Federation, as part of a newborn screening (NBS), all newborns have been examined for spinal muscular atrophy 5q (SMA). In the Krasnodar region, the center for the implementation of this program is the Scientific Research Institute – Ochapovsky Regional Clinical Hospital No. 1. The purpose of this study is to evaluate the frequency and molecular features of SMA identified in newborns of the Krasnodar region as part of the NBS for the period 2023-2024.The research material was samples of dried blood spots. The studies were carried out using the polymerase chain reaction method in real time. From January 1, 2023 to December 31, 2024, 103,513 children were examined in the Krasnodar region, among whom the diagnosis of SMA was confirmed in 14 children. The distribution of the number of copies of the SMN2: 2 copies – 3 children, 3 copies – 7 children, 4 copies – 4 children. Thus, the frequency of SMA in the Krasnodar region is 1:7394.

Breast tumor contains various cell types, including cancer stem cells, a small proportion of which survive chemotherapy and lead to recurrence or metastasis. With this in mind, the aim of the study is to evaluate the prognostic potential of the stem cell epigenetic index. 19 luminal B breast cancer samples were used for statistical analysis and deconvolution. Comparison of samples with and without metastasis showed a statistically significant (p < 0.05) predominance of the index in samples without metastasis, and survival curve analysis showed a significant increase (p < 0.05) in metastatic-free survival associated with high index. The results obtained allow using the epigenetic index of stem cells as a prognostic marker for metastasis-free survival.

The detection of copy number variations (CNVs) of single genes using molecular genetic methods has created a need to develop an algorithm for their clinical interpretation. This report presents the main stages, features and complexities of interpreting the pathogenic significance of single-gene CNVs.

Homologous recombination repair deficiency (HRD) is involved in the development of high-grade serous ovarian carcinoma (HGSOC) and its higher sensitivity to platinum-based chemotherapy. We have evaluated the HRD status, including BRCA mutations, genomic scar score, and methylation of BRCA1 in 352 HGSOCs. We then divided the HRD-positive cohort into molecular subgroups, the BRCA mutation cohort and BRCA1 methylation cohort and evaluated their first-line chemotherapy response and progression-free survival (PFS). The BRCA mutation group showed the best outcome in platinum therapy (ORR 96%), and the highest median PFS (46 months). Patients with BRCA1 methylation showed a significantly poorer outcome, with a median PFS of 19 months and a significantly lower ORR to platinum therapy (84%). In conclusion, methylation group had poor outcomes in terms of chemotherapy response, and PFS, requiring a more thorough follow-up.

Introduction. Ectodermal dysplasia (ED) represents a heterogeneous group of genetic disorders associated with impaired development of ectodermal structures. The most common form is X-linked hypohidrotic ectodermal dysplasia (XLHED), caused by mutations in the EDA gene, which encodes ectodysplasin A, a key protein involved in the development of ectodermal tissues. Due to the X-linked inheritance pattern, males are more frequently affected; however, female carriers may also exhibit clinical manifestations. The phenotypic variability in females has traditionally been attributed to skewed X-chromosome inactivation (XCI), though this hypothesis remains controversial.

Objective: The aim of this study was to analyze XCI patterns in female carriers of EDA mutations and assess their correlation with the severity of clinical manifestations.

Methods. The study was conducted on 47 female patients using methylation-sensitive PCR and analysis of repeats in the AR gene.

Results. The obtained data did not reveal a statistically significant correlation between the degree of XCI and the severity of HED symptoms (p = 0.277).

Conclusion. This study confirms that the analysis of XCI in blood is not a reliable predictor of disease severity in females with X-linked HED and, therefore, should not be recommended for diagnostic purposes or reclassification of variants of uncertain significance in the EDA gene.

MODY (Maturity onset diabetes of the young) is a group of non–immune genetic disorders of carbohydrate metabolism caused by variants of genes associated with the synthesis, secretion or action of insulin. There are 14 subtypes of MODY. GCK-MODY (69.7%) and HNF1A-MODY (10.1%) are the most common subtypes according to the registry of the Institute of Pediatric Endocrinology of the Endocrinology Research Centre, Moscow, Russia. Rare subtypes of MODY were used in 9.4% of cases. 1.1% patients have variants in MODY candidate genes. 6.7% of patients were diagnosed with MODYX. Verification of the genetic cause plays a key role in the choice of therapeutic tactics and opens up prospects for the use of gene therapy in such patients in the future.

Lysosomal storage diseases (LSD) are a group of rare disorders caused by impaired lysosomal function, characterized by a deficiency in the activity of lysosomal enzymes and accumulation of their substrates. It is assumed that cells can facilitate the accumulation of substrates through exocytosis and changes in extracellular vesicle (EV) biogenesis, leading to changes in their morphology and size. EVs are membrane objects less than 1000 nm in size that perform various biological functions, such as the transport of biologically active molecules (proteins, lipids, microRNAs, mRNAs, and DNA) and intercellular interaction. The role of these objects in health and disease is actively being studied for potential use as biomarkers or therapeutic purposes. Objective: to evaluate the morphology and size of plasma EVs in LSD using cryo-electron microscopy. The study included patients with LSD, including patients with Gaucher disease, Fabry disease, Niemann-Pick disease and controls. EVs were isolated from blood plasma samples using ultracentrifugation. For the first time, the morphology and size of plasma EVs in patients with LSD were characterized using cryo-electron microscopy. Based on the results of analysis, it was found that the plasma EVs of LSD patients are characterized by complications in vesicle morphology, as well as the presence of electron-dense cargo. Plasma EVs from a patient receiving substrate-reducing therapy for Gaucher disease are also characterized by an increase in vesicle size compared to controls. Our results indicate changes in the biogenesis and composition of blood plasma EVs in LSD.

Severe hypertriglyceridemia (HTG) is a lipid metabolism disorder characterized by an increase in the level of triglycerides (TG) in blood plasma ≥10 mmol/l. The occurrence of pathology is caused by environmental factors, lifestyle and genetic determinants [1]. Using the example of two clinical cases, the article describes the diagnosis of severe HTG using molecular genetic methods, as a result of which variants in the LMF1 and LPL genes were identified. Genetic examination of patients with hypertriglyceridemia contributes to the differential diagnosis of the disease, helps to establish the hereditary nature of the pathology and select therapy.

Bone fractures may be observed in various hereditary diseases, including rare ones – gnathodiaphyseal dysplasia and Grange syndrome. We present a description of two patients with frequent fractures: a 12-year-old girl with gnathodiaphyseal dysplasia associated with the previously described c.1538C>T variant in the ANO5 gene, and an 11-year-old boy with new compound heterozygous variants c.1564C>T and c.2117_2118del in the YY1AP1 gene and the Grange syndrome phenotype. Both patients had frequent pathological bone fractures on the background of osteoporosis. Both children had normal intelligence. The phenotype of the child with Grange syndrome included variable fracture localization, moderate brachydactyly, delayed bone age, mitral valve prolapse, labile systolic hypertension, hyperactivity, and attention deficit disorder. In this case particular attention was paid to the cardiovascular system. The patient with gnathodiaphyseal dysplasia predominantly suffered from vertebral fractures. Thus, the presented clinical observations indicate the need to include gnathodiaphyseal dysplasia and Grange syndrome in the differential diagnostic series when osteogenesis imperfecta is suspected.

Data on the assessment of the cytokine level in the blood as a marker for the diagnosis and progression of non-alcoholic fatty liver disease (NAFLD) are contradictory; the level of mRNA of their genes in peripheral blood leukocytes (PBL) has not been considered as such. The aim of the work was to assess the level of TNFα, IL6 in blood plasma and mRNA of the coding genes in PBL as markers of the transformation of liver steatosis (LS) into non-alcoholic steatohepatitis (NASH) in NAFLD. The analysis of the levels of TNFα, IL-6 and the TNFA, IL6 genes mRNA in the blood of patients with early forms of NAFLD (LS (n=30), weak activity NASH (-WA) (n=33), F1-F2) and in the control (n=35) was carried out. The concentrations of TNFα and IL6 in the blood in LS and NASH-WA do not differ, but are elevated compared to the control. For the first time, it was shown that the levels of the TNFA and IL6 genes mRNA in PBL in NASH-WA are higher than in LS, correlate with each other and are diagnostically significant for detecting NASH among LS patients. According to the ROC analysis of the levels of blood parameters in NASH-WA patients relative to LS, AUC (TNFA mRNA) = 0.973 95%CI 0.925–1.000, p< 0.001; AUC (IL6 mRNA) = 0.769 95%CI 0.634–0.957, p = 0.005. The levels of the TNFA and IL6 genes mRNA can be considered as markers of LS transformation into NASH.

Biallelic mutations in the GBA1 gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase), are a common high-risk factor for Parkinson’s disease (PD). Pharmacological chaperones (PCs) are being developed as an approach to treating of PD associated with mutations in the GBA1 gene. Using high performance liquid chromatography coupled with tandem mass spectrometry, we evaluated the enzymatic activity of GCase and the concentration of its substrate, hexosylsphingosine (HexSph), in brain tissue of the C57BL/6 mouse after administration of PCs GCase (ambroxol and N2). We showed an increase in GCase activity and a decrease in HexSph concentration in the brain tissue of mice treated with PCs GCase. For the first time, we have demonstrated the efficacy of PCs GCase N2 in brain tissue from C57BL/6 mice.

Schizophrenia is a polymorphic and polygenic disorder that affects all aspects of a patient’s life. Objective: To study how the polygenic scores of schizophrenia risk (SZ-PRS) are associated with the level of education and labor adaptation in patients with schizophrenia. Methods: The sample consisted of 829 patients diagnosed with schizophrenia or schizophrenia spectrum disorders. Data on the level of education and employment were available for all participants. The polygenic score of schizophrenia risk (SZ-PRS) calculated as a weighted sum of single nucleotide polymorphisms that were associated with schizophrenia in a genome-wide association study was used as an indicator of genetic predisposition to schizophrenia. General linear models were used in statistical analysis. The results of the study showed that higher SZ-PRS predicted worse employment (p=0.003) and lower educational level (p=0.09) in women, but not in men. Conclusions: The study demonstrates for the first time that genetic predisposition to schizophrenia can negatively affect patients social functioning, thereby impairing their quality of life.

This study presents the results of a clinical-genetic analysis conducted on a cohort of 350 pediatric patients with hereditary systemic skeletal dysplasias. Diagnosis was confirmed using a variety of molecular genetic methods, including massively parallel sequencing. The findings provide a detailed analysis of the prevalence and genetic spectrum of monogenic hereditary systemic skeletal dysplasias in Russian patients. Furthermore, a strategy for clinical and molecular genetic diagnosis of hereditary systemic skeletal dysplasias in pediatric patients has been developed, significantly improving the ability to identify the molecular cause of the disease.

Functional analysis of mutational changes in genes in model systems in vitro plays a key role in understanding the molecular mechanisms of hereditary pathologies and is an important criterion for confirmation the pathogenicity of a particular variant. Pathogenic variants of the GJB2 gene encoding the transmembrane protein Cx26 are one of the most common causes of hearing loss in many human populations. Previously, based on the HeLa cell line, we obtained subclonal lines with a knockout of the GJB2 gene using the CRISPR/ Cas9 system. One of them served as the basis for generating transgenic cell lines with constant expression of a number of mutant GJB2 variants identified in patients with hearing loss. The aim of this work is to characterize and further develop a panel of transgenic HeLa cell lines stably expressing various variants of the GJB2 gene for comparative functional analysis of the effects of mutant GJB2 variants on the structure and functions of the Cx26 protein. Taking into account the features of the «life cycle» of the Cx26 protein, the approaches have been defined and a set of experimental methods have been developed to assess the expression of mutant GJB2 variants, to assess the intracellular localization and ability of mutant forms of the Cx26 protein to form functional hemichannels/channels.

Osteogenesis imperfecta (OI) is a genetically heterogeneous group of disorders characterized by reduced bone mineral density, resulting in increased bone fragility and pathological fractures. Advanced molecular genetic diagnostic methods now enable precise identification of genetic variants and specific OI forms, thereby optimizing clinical management and diagnostic strategies. The objective of this study was to analyze clinical and genetic characteristics of monogenic isolated and syndromic forms of OI to enhance their differential diagnosis. A total of 423 patients from 290 unrelated families were examined using clinical-genealogical assessment and comprehensive molecular genetic techniques, including targeted sequencing, exome sequencing, genome sequencing, and Sanger sequencing. An etiological factor was successfully identified in 94.7% of the patients, with 202 nucleotide variants detected across 11 genes; notably, 80 variants were novel. Autosomal dominant forms of OI associated with mutations in the COL1A1 and COL1A2 genes comprised 83.3% of the entire cohort. The study determined the prevalence and detailed clinical-radiological features of rare genetic variants linked to the IFITM5, SERPINF1, P3H1, FKBP10, and BMP1 genes. Furthermore, recurrent nucleotide variants were identified in the IFITM5, SERPINF1, SGMS2, and FKBP10 genes. The findings have allowed the refinement of clinical and molecular genetic diagnostic approaches, significantly contributing to improved genetic counseling and clinical management of patients with various forms of OI.

Introduction. The manifestation of monogenic causes of familial hypercholesterolemia (FH) is influenced not only by lifestyle but also by polygenic background and additional variants in lipid metabolism genes.

Aim. To study the dependence of low-density lipoprotein cholesterol (LDL-С) levels on polygenic background and variants in lipid metabolism genes in patients with causal variants in LDLR, APOB, PCSK9 genes.

Materials and methods. The study was conducted on 432 patients: 364 with variants in LDLR gene, 68 carriers of APOB variant, and two carriers of PCSK9 variant.

Results. Significant correlations of LDL-C levels in patients with variants associated with FH with polygenic background based on the data of genetic risk scores were established.

Conclusions. When predicting the further course of FH, it is necessary to take into account not only the identified monogenic causes, but also the patient’s genetic features.