Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a rare autosomal recessive disorder of long-chain fatty acid betaoxidation, resulting from mutations in the ACADVL gene. The disease exhibits a heterogeneous phenotypic spectrum, ranging from asymptomatic cases to severe neonatal forms, and is associated with a high risk of a lethal outcome in the absence of treatment. As of January 1, 2023, VLCADD has been included in the expanded neonatal screening program in the Russian Federation. 1,231,401 newborns born in the Russian Federation between January and December 2023, and 1,199,015 newborns born between January and December 2024 were screened during the expanded neonatal screening program. Primary neonatal screening (24-48 h of life) conducted in regional centers of the Russian Federation identified 4342 newborns with elevated levels of tetradecenoylcarnitine (C14:1) in their blood, categorizing these patients as being at risk for VLCADD. Confirmatory diagnostics at the Research Center for Medical Genetics involved remeasuring acylcarnitine concentrations in the blood using tandem mass spectrometry (MS/MS), as well as a molecular genetic analysis of the coding region of the ACADVL gene (NM_000018.4). During the confirmatory biochemical diagnostics, an increase in blood C14:1 level was detected in 35 patients. VLCADD was confirmed at the molecular genetic level in 22 patients. The cumulative incidence of VLCADD in the Russian Federation was estimated to be 1 in 110,473 live births (95% CI: 1:1:72,123 — 175,963). This article presents the clinical, biochemical and molecular genetic characteristics of 22 patients diagnosed with VLCADD during the first two years of expanded neonatal screening in the Russian Federation.

Background. Lynch syndrome is a hereditary cancer syndrome associated with an increased risk of colorectal and endometrial cancer, as well as other, less common tumors. Identification of pathogenic variants, associated with Lynch syndrome, via genetic testing provides an opportunity of genetic counseling not just for the patient but also for their relatives. Genetic diagnostics for hereditary cancer syndromes in all family members has the advantage of enabling preventive measures for early diagnosis and further disease progression. This is particularly important for patients with a family cancer history. Current sequencing technologies allow analysis of not only known variants, but also previously undescribed ones.

Aim: to present a clinical case of Lynch syndrome caused by a previously undescribed likely pathogenic variant of the MLH1 gene.

Methods. The results of molecular diagnostics for the genetic cause of Lynch syndrome are presented. The proband underwent wholegenome sequencing, followed by Sanger sequencing. The proband’s relatives only underwent Sanger sequencing.

Results. The clinical case described shows a likely pathogenic variant in the MLH1 gene: chr3:37017551delT (hg38), p.Val279GlyfsTer18. Sanger sequencing was used for validation. Segregation analysis was carried out.

Conclusion. Next-generation sequencing, particularly whole-genome sequencing, allows for the analysis of all candidate genes and the identification of rare variants, including those that have not been described in the literature, that are potentially associated with disease. Timely identification of causative variants informs treatment and observation of patients. It also enables the examination of first- and second-degree relatives and provides recommendations for cancer prevention and screening.

Introduction. Сystic fibrosis (CF) is characterized by pronounced genetic heterogeneity and, in this regard, clinical variability, occurs in all countries of the world, but there are pronounced population differences in its frequency with decreasing gradient of distribution from North to South and from West to East of Eurasia.

Aim: the study of regional clinical, genetic and epidemiologic features of CF for the development of optimal algorithms for diagnosis and treatment of the disease is relevant.

Patients and Methods. The molecular genetic study included 1403 people, including family members, control and population samples, observed from 1998 to 2023 in the Republican Medical and Genetic Center (Ufa). Clinical and laboratory and molecular genetic methods of research, bioinformatic processing of NGS sequencing results were used.

Results. Genetic heterogeneity of CF by spectrum and frequencies of pathogenic changes in CFTR gene in ethnic groups of RB was revealed; mutations 3849+10kbC->T, p.[G509D;E217G] are specific for patients of Tatar and Bashkir ethnicity, 394delTT and p.[S466X;R1070Q] – for Tatars.

Conclusion. Introduction of molecular genetic technologies, allowed to develop an effective algorithm of DNA-diagnosis of the disease.

Proteins with chaperone properties play an important role both in the risk of developing ischemic stroke (IS) and in protecting cells under ischemic conditions. The aim of this work was to analyze the associations of polymorphic variants of the Hero genes (SERBP1, SERF2, C19orf53, C11orf58, C9orf16) with the risk of developing and clinical manifestations of IS. It was found that the association of Hero SNPs with IS is characterized by sex-specific effects and is also significantly modulated by environmental risk factors. Functional annotation of SNPs showed that the molecular mechanisms of the association of Hero genes with IS are due to their participation in the regulation of neuro- and angiogenesis, apoptosis, oxidative stress, hypoxia and inflammation.

In a brief report, the results of an analysis of genetic differentiation among five populations of Dagestan belonging to two language branches are presented, based on 15 X-STR markers used for DNA identification.

The marriage structure of married couples was studied during reproductive genetic screening for carriage of hereditary diseases. The marriage structure was assessed based on the data on the ethnicity and place of birth of the spouses. Marriage migration processes are limited to the territory of Yakutia. Monoethnic Yakut marriages are most common. A positive value of marriage assortativity was obtained among the Yakuts. A high frequency of heterozygous carriage of autosomal recessive diseases was revealed. Genetic screening throughout the republic is necessary for their prevention.

The clinical and genetic characteristics of 9 cases of hyperphenylalaninemia (HРA) identified during the extended neonatal screening (RNC) for the period 2023-2024 are presented. With confirmatory diagnosis using tandem mass spectrometry and molecular genetic analysis of HPA-associated genes, 5 children were diagnosed with severe HPA and 4 with mild HPA. All patients with severe HPA had mutations in the PAH gene: a frequent mutation C.1222C>T in the homo or hemizygous state (in 3 children), a combination of two pathogenic nucleotide variants in the compound heterozygous state (in 2 children). Three children with mild HPA had mutations in the PAH gene in a compound heterozygous state: a frequent mutation and a rare one (1 child); a frequent mutation and a mutation with unknown clinical significance (1 child), two rare mutations (1 child). One child with mild HPA had 2 mutations in the PTS gene in a compound heterozygous state. All children (both with severe HPA receiving treatment and with mild HPA, have.

Familial hypercholesterolemia (FH) is a common genetic disease characterized by high levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in blood. Despite the high prevalence of FH in the world and in Russia, the problem of insufficient detection of FH remains urgent, which leads to a higher incidence of early cardiovascular diseases in the risk group. The purpose of this work was to utilize targeted NGS-sequencing technology for the systematic screening of FH. A new familial case of FH associated with a pathogenic variant in exon 14 of the LDLR gene (p.Cys677Tyr) has been described. Proband: female, 30 years old, clinical diagnosis of FH, 15 points according to the diagnostic criteria of the Dutch Lipid Clinic Network. The initial level of LDL-C was 8,7 mmol/L, and LDL-C decreased to 3,1 mmol/l after appropriate therapy (rosuvastatin 10 mg+ezetimibe 10 mg). The prevalence of FH with insufficient diagnosis of the disease remain a significant problem in Russian medicine.Targeted NGS-panels are an economically feasible tool, while showing high efficiency in identifying patients with FH.

Background. Conventional cytogenetic studies reveal chromosomal abnormalities in approximately 40% of uterine leiomyomas (ULs). ULs with a normal karyotype comprise minor cell subpopulations with numerical abnormalities of chromosomes 7 and 16 (so-called heteroploidies). Aim: to screen ULs with an abnormal karyotype, cultured in a medium with and without estrogen and progesterone supplementation, for cells with numerical abnormalities of chromosomes 7, 16 and X.

Methods. The frequency and the spectrum of heteroploidies in nine ULs with an abnormal karyotype, cultured in a medium with and without supplementation of estrogen and progesterone, were studied by interphase FISH using DNA probes to DXZ1, D7Z1, D16Z3 loci of chromosomes X, 7 and 16, respectively.

Results. Small populations of tetraploid cells and cells with monosomies X, 7 or 16 were detected in all UL cultures. The total frequency of heteroploid cells in UL cultures varied from 0.8 to 9.1%; tetraploid cells were predominant over monosomic cells, and cells with monosomy 7 – over monosomies 16 or X. The spectrum and the frequency of heteroploidies did not differ between UL samples cultured with and without hormones.

Conclusions. Small populations of tetraploid and monosomic cells are characteristic of cultured ULs not only with normal but also with an abnormal karyotype. The addition of estrogen and progesterone to the culture medium does not affect the frequency and the spectrum of heteroploidies.

Impaired stability of carotid artery atherosclerotic plaques (CAAP) is associated with changes in miR-143/145 expression. In some tissues, the miR-143/145 expression is regulated by CARMN (MIR143HG) promoter methylation, however, it is possible that methylation in the promoters of the MIR143 and MIR145 genes, which are located in the CARMN gene body, may be influenced. As a rule, there is a negative correlation between methylation in promoter regions of genes and their expression. The aim of our study was to analyze the association of miR-143/145 expression with the methylation level of CpG sites in CARMN gene in CAAPs. DNA and microRNA for analysis were extracted from CAAPs of patients with advanced carotid atherosclerosis (n=14). DNA methylation analysis was performed by MethylChip, and microRNA expression was analyzed using the microRNA-seq method. We revealed an inverse correlation of miR-145-3p and miR-143-3p expression with methylation of cg01726320, cg01558401 and cg26585864 in the CARMN promoter and a direct correlation with methylation of cg04317047, cg16684117 and cg21242144 in the CARMN gene body and in the MIR143 and MIR145 promoters. These results suggest an important role of CARMN promoter methylation in the regulation of miR-143/145 expression in carotid atherosclerosis.

Currently, there are data on an association between chromosome instability and neurodevelopmental diseases. Here, we report a comparative analysis of two cases presenting with chromosome instability, mental disorders and similar history studied by cytogenetic and molecular cytogenetic techniques (SNP-array).We show that an increase of chromosome instability is associated with negative dynamics of the disease. SNP-array with bioinformatic analysis revealed genomic variations causing the formation and increase of chromosome instability.

Background. Since 2023, the Russian Federation has implemented an expanded neonatal screening program, incorporating molecular genetic diagnostics for phenylketonuria (PKU)/ hyperphenylalaninemia (HFA) in newborns with elevated phenylalanine levels. The analysis of a large-scale group of patients collected from all regions of Russia will allow the identification and evaluation of a wide range of allelic variants of the PAH gene.

Methods. 1254 dried blood spots on filter paper and whole blood samples in EDTA tubes were collected from newborns who, during screening by tandem mass spectrometry (TMS), showed elevated levels of phenylalanine (>120 µmol/L), phenylalanine/tyrosine ratio (>3 µmol/L) on the 2nd day of life or later. A repeat analysis by TMS was performed for these newborns, alongside an analysis of 25 common variants using allele-specific MLPA (1252 probands). In cases where one pathogenic variant was identified in the PAH gene and/or repeated elevation of phenylalanine levels was observed, subsequent panel-based NGS sequencing (genes: PAH, PTS, QDPR, GCH1, PCBD1, SPR, DNAJC12) and quantitative MLPA analysis were conducted.

Results. Among 540 newborns (1080 chromosomes), two or more pathogenic variants in the PAH gene were identified. For five probands, two variants were detected in genes associated with the development of hyperphenylalaninemia (HPA). The frequency of molecularly confirmed PKU in the Russian Federation was 1:4501, which differs from the previously estimated frequency of 1:7000.

Timely referral of a patient for genetic counseling for breast cancer allows you to adjust treatment tactics and take preventive measures. A 29-year-old patient with breast cancer and a family history on her mother’s side was consulted. Given the absence of frequent pathogenic variants in the BRCA1 and BRCA2 genes, panel targeted sequencing was performed. According to the test results, a pathogenic variant C.844C>T (p.Arg282Trp) was identified in exon 8 of the TP53 gene in a heterozygous form associated with the development of Li-Fraumeni syndrome. Validation of the result was performed by Sanger sequencing.

Taking into account the hereditary nature of the disease, as well as the existing risk of developing primary multiple breast cancer, a surgical intervention was performed in the amount of a radical bilateral subcutaneous mastectomy with simultaneous reconstruction with endoprostheses and a biopsy of the sentinel lymph node on the left. Radiation therapy was not performed due to the high probability of radiation-induced cancer in this syndrome. Thus, the referral of the patient for genetic counseling and subsequent DNA diagnostics made it possible to adjust the treatment and take preventive measures.

The aim of this study was to select and define a list of hereditary diseases in the Yakut population for pilot molecular genetic screening for major mutations in prenatal and neonatal screening programs.. 17 diseases and major mutations were identified, 13 of which can be included in the list of candidate genes of hereditary diseases for the Molecular Genetic Screening Program within the framework of expanded neonatal or early prenatal screening programs.

This study aimed to investigate the expression of IL20RB and SELENOP genes in peripheral blood leukocytes (PBL) of patients with pulmonary sarcoidosis. Fifty-two people were enrolled in our study, 24 of whom were patients (average age 42.11±2.21 years) with an established diagnosis of pulmonary sarcoidosis, chronic course, stage II, not receiving therapy. The diagnosis was established in accordance with the criteria based on clinical, radiological and laboratory changes with histological verification of the biopsy study. The control group was formed by 28 conditionally healthy donors (average age 43.03±1.84 years). The level of IL20RB, SELENOP gene transcripts in the studied groups was estimated by real-time PCR. According to our data, the level of IL20RB gene mRNA expression in PBL of patients with pulmonary sarcoidosis was lower compared to the control (p=0.0001). The number of SELENOP gene transcripts was significantly different from the values in the control group (p=0,0004). The results of the study may indicate the probable involvement of this genes in the pathogenesis of pulmonary sarcoidosis.

Introduction. Mutations in the STRC gene are the second main cause of congenital bilateral mild to moderate hearing loss after mutations in the GJB2 gene.

Objective: to assess the prevalence of the autosomal recessive form of DFNB16, medical history and results of audiological examination in children with mutations in the STRC gene.

Methods. Analysis of medical records of children born between 2008 and 2023, registered at the children’s audiological center, audiological and otolaryngological examination, analysis of the results of genetic studies.

Results. Medical records of 1256 children with bilateral hearing loss of I and II degrees were analyzed. Genetic examination was performed on 540 children (43%). In this group, mutations in the GJB2 gene were confirmed in 44% of the examined patients, in the STRC genein 8%, in the USH2A gene – in 2%. The median age of children with DFNB16 at the initial visit to an audiologist was 48 months. 50% of children «failed» the hearing screening, 30% had the result «passed», and in 20% of cases, screening in the maternity hospital was not performed. According to the initial tonal threshold audiometry, the average hearing threshold at frequencies of 0.5-4 kHz was 45.8 dB, during the repeated examination – 42.8 dB.

Conclusions. DFNB16 occurs in 8% of cases among children with mild to moderate bilateral sensorineural hearing loss. The presence of concomitant ENT pathology increases the average age of contacting an audiologist and conducting genetic studies.

It is known that in the atmosphere of coal production a number of carcinogenic factors arise that cause a negative impact on the genetic stability. In this regard, it is necessary to determine genotoxic effects in workers of coal-fired thermal power plants. The work studied the influence of the production environment of coal-fired thermal power plants on the epigenetic regulation of the XRCC1, XRCC2, XRCC3, XRCC4 genes in 455 workers of coal-fired thermal power plants in the city of Kemerovo compared with 533 non-working residents of the same region. The methylation status of the promoters of the studied genes was assessed using methyl-specific polymerase chain reaction. The influence of the industrial environment on the change in the effect of methylation of the promoters of all studied genes in producers was established.

Galactosemia is an autosomal recessive hereditary disease associated with a violation of the conversion of galactose into glucose. Galactose is one of the main sugars present in human milk and enters the newborn’s body during the first hours of life. For this reason, early diagnosis of galactosemia is a priority. The objective of this study was to develop a technology consisting of domestic reagents for early diagnosis of galactosemia by measuring total galactose in dry blood spots (DBS). The technology is based on the enzymatic oxidation of galactose to galactonate by galactose dehydrogenase, in which NAD⁺ is reduced to NADH. The fluorescence intensity of NADH is measured, and the results are recorded. The conversion of galactose-1-phosphate, present in erythrocytes, to galactose is catalysed by the enzyme alkaline phosphatase. Regulations and instructions for the kit have been developed. The development of strains capable of producing galactose dehydrogenase and alkaline phosphatase has also been undertaken. These enzymes are capable of being stored for extended periods in lyophilized form and exhibit high activity after reconstruction in buffer solutions. The novel technology exhibits comparable precision in galactose quantification to its analogous counterparts, yet it employs an alternative reagent foundation.

The study provides a comprehensive molecular cytogenetic characterization of a de novo derivative X chromosome exhibiting a terminal deletion of the short arm and a terminal duplication of the long arm in a female patient presenting with an abnormal phenotype. The potential mechanisms that may underlie the formation of this chromosomal abnormality, as well as the contribution of chromosomal imbalance in clinical manifestations, are discussed.

A clinical case of Wilson-Konovalov disease in combination with chronic viral hepatitis C in a 36-year-old patient is presented. The article contains the dynamics of the patient’s condition from the moment of diagnosis of the disease to the present, data from instrumental and laboratory studies, and treatment of the patient.

Nijmegen breakage syndrome is an autosomal recessive DNA repair disorder from the group of combined primary immunodeficiency (PID) or Inborn Errors of immunity (IEI), characterized by a well-defined phenotype (microcephaly), high frequency of infectious complications and predisposition to cancer. 99% of NBS cases in RF are associated with «Slavic» deletion c.657_661delACAAA in NBN gene in homozygous state in unrelated families. Due to the high risks of life-threatening complications patients benefit form hematopoietic stem cell transplantation received before malignancy. The study presents a case of a screen-positive (low TREC, KREC levels) newborn with microcephaly, quickly diagnosed with NBS and significantly delayed diagnoses in a case of his elder sister with the same phenotype. The neonatal screening (NS) program implementing TREC/KREC opens up opportunities for timely diagnosis and treatment of rare diseases, and also familial genetic counselling. Keywords: Nijmegen syndrome, TREC/KREC, expanded neonatal screening, congenital immune defects, immunodeficiency.

Human endogenous retroviruses (HERVs) are the consequences of retrovirus infections that have integrated into the human genome and have been preserved throughout evolution. The HML2 subgroup is a part of the HERV-K family and maintains activity in certain types of cells. The aim of the study is to assess the expression of HML2 in samples of normal and tumor tissues of patients with colorectal cancer (CRC) using several bioinformatics tools and compare the results.

The study analyzed RNA-Seq data from 48 samples obtained from 12 patients diagnosed with CRC. Three bioinformatics tools were used for the analysis of HML2 expression: GeneTEFlow, TECount, and Telescope. Differential expression was assessed using the DESeq2 package. In our study, we also performed verification of detected transpositions in genomic data using the MELT tool. All loci showing expression based on transcriptomic data were confirmed in the genomic data.

Loci with increased HML2 expression were identified in CRC samples: 1q22, 7p22.1, 8p23.1, 10q24.2, 11q12.1, 11p15.4b, 9q34.11, 19q13.41, and 22q11.23. These loci contain enhancers and genes that regulate cellular metabolism, inflammation, and immune response. The results indicate increased HML2 expression in CRC samples, which may suggest the involvement of these mobile genetic elements in carcinogenesis. To improve the accuracy and depth of the study, it is important to use several bioinformatics tools and analyze overlapping output data, which allows to minimize potential errors and increases the reliability of the results.

Plaque (lamellar) ichthyosis (LI) (OMIM: 606545) is a severe, autosomal recessive, genetically heterogeneous skin disease characterized by severe hyperkeratosis, large, plate-like dark scales, and generalized erythroderma. LI usually presents from birth or in the first few months of life and has a progressive course. The clinical differentiation between LI and other forms of congenital ichthyosis poses a significant challenge due to the substantial number of overlapping symptoms, which complicates the diagnostic process. This study aims to elucidate the clinical manifestations of congenital ichthyosis, with a particular focus on the dermatological presentations observed in two patients. Whole genome sequencing was performed. In both cases, the same pathogenic nucleotide sequence variant in exon 7 of the ALOXE3 gene was identified, in one case in a compound-heterozygous state and in another in a homozygous state, that confirmed the diagnosis of LI. Making a definitive and accurate differential diagnosis of autosomal recessive congenital ichthyosis (ARCI) forms acquires an integrated multidisciplinary approach that combines epidemiologic, clinical, and genetic data. That also could provide novel insights into the nature of the disease and could help to develop mutation screening strategies.

Background. Predicting the outcomes of assisted reproductive technology (ART) cycles in couples where one of the spouses is a carrier of chromosome translocations is of importance.

Objective: to determine how the type of chromosomal translocation and carriers gender affect the embryological stage of ART cycles in a couple where one of the spouses is a carrier of a reciprocal or Robertsonian translocation.

Methods. The analyzed data included 137 embryological protocols of ART cycles of 100 couples, in which one of the spouses was a carrier of a reciprocal (31 women and 27 men) or Robertsonian translocation (21 women and 21 men).

Results. The effect of the translocation type and the carrier gender on the efficiency of fertilization and preimplantation development of embryos was analyzed. In the Robertsonian translocation carriers, the frequency of bipronuclear zygotes and the ability of embryos to develop up to day 3 are higher when a carrier is a female (U=490, p=0.024 and U=476, p=0.044, respectively). When a carrier is a man, the frequency of bipronuclear zygotes and the ability of embryos to develop up to day 3 were significantly higher in the case of reciprocal compared to Robertsonian translocation (84.6% versus 75%, U=528, p=0.017 and 59.5% versus 50%, U=512, p=0.034, respectively), which indicates negative selection of embryos before the day 3 specifically in male-carriers of Robertsonian translocation. The ability of embryos to develop up to the day 5 did not differ statistically significantly between the study groups (Mann-Whitney test, p>0.05).

Conclusion. The results of the embryological stage of ART cycles in couples in which one of the spouses is a carrier of a chromosomal translocation are characterized by the lowest values for male-carriers of the Robertsonian translocation.

The discovery of microRNA (miRNA) provides a new and powerful tool for studying malignant tumors of various localizations. Objective: to study aberrant methylation of individual miRNA genes in ovarian cancer (OC). Material: 25 paired samples (tumor/norm) of OC, as well as 15 control ovarian tissue samples. Methods: MS-HRM analysis. We have obtained for the first-time information on the methylation level of miRNA genes miR-663a and miR-663b in OC. The results of the study indicate a specific involvement of miRNA genes miR-663a and miR-127 in the pathogenesis of OC.

Pitt-Hopkins syndrome is a rare autosomal dominant disorder characterized by multiple pathological manifestations, including intellectual disability, speech impairment, significant cognitive and motor developmental delays, and distinctive facial dysmorphisms. The condition is caused by alterations in the nucleotide sequence of the TCF4 gene, which encodes a transcription factor critical for nervous system development and function. Although the spectrum of pathogenic variants in TCF4 has been well characterized, their asymptomatic carriage remains poorly documented in the literature. In this study, using the ClinVar and gnomAD databases, we identified seven pathogenic or likely pathogenic variants in healthy individuals: rs1568303086, rs751190049, rs121909121, rs863224934, rs1230192802, rs895426748, and rs1603624808. These findings highlight the need for functional analysis and potential reclassification of the rs1230192802 variant. The observed cases underscore the variable expressivity of TCF4 variants.

Background. Telomeres are the terminal regions of chromosomes that play a crucial role in cellular aging and maintaining genomic stability. While telomere length decreases with age in somatic cells, an opposite trend is observed in spermatozoa. However, information on how telomere length changes during human spermatogenesis and its relationship with age remains incomplete.

Objective: To analyze the changes in telomere length during the differentiation of spermatogenic cells and to evaluate its association with the age in azoospermic patients.

Methods. The study was performed on testicular biopsy samples from 34 azoospermic patients aged 24-60 years. Cytogenetic preparations of colchicine-treated mitotic and meiotic metaphase plates were obtained from the samples. Telomere length was measured using quantitative fluorescence in situ hybridization (Q-FISH) on chromosomes from spermatogonia (n=483), spermatocytes I (n=305), and spermatocytes II (n=396).

Results. The telomere length in spermatogonia was shorter than in spermatocytes I (p=0.0234), and the telomere length in spermatocytes I was shorter than in spermatocytes II (p=0.0107). A positive correlation was observed between telomere length in spermatocytes II and the patients’ age (ρ=0.3966; p=0.0496). No association was found between the patients’ age and telomere length either in spermatogonia or in spermatocytes I (ρ=0.0643; p=0.7177 and ρ=-0.03297; p=0.8531, respectively).

Conclusion. Thus, in azoospermia, telomere length in spermatogenic cells increases from spermatogonia to spermatocytes I, and then to spermatocytes II; in spermatocytes II, it also increases with the patients’ ageing.

Pathogenic variants of the NBAS gene cause an autosomal recessive hereditary disease associated with a wide range of symptoms affecting the liver, skeletal, and nervous system. Recently, a less than 100 patients have been described who have attempted to uncover the phenotype-genotype correlation. We present a clinical description of a patient with a clinical phenotype combining symptoms of SOPH syndrome (OMIM# 614800) and isolated acute liver failure type 2 (ILFS2, OMIM#616483). Biallelic pathogenic variants of the NBAS gene NM_015909.4:c.686dupT; p.(Ser230Glnfs*4) and the missense variant NM_015909.4:c.5741G>A; p.Arg1914His gene were identified using whole-exome sequencing (WES). The variants were validated using the Sanger sequencing method, and their transposition was proved.

The paper presents the results of a study of genetic variants F2 G20210A, F5 G1691A, F7 G10976A, F13A G103T, FGB G-455A, ITGA2 C807T, ITGB3 T1565C and SERPINE1 5G-6754G associated with hemostasis disorders in a cohort of patients who sought medical care at the Almazov National Medical Research Center from 2018 to 2022.

Background. Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant disorder related to expansion diseases. A new method for the prevention of SCA1 is PGT-M (preimplantation genetic testing for monogenic diseases).

Purpose. Analysis of the change in the number of trinucleotide repeats in embryos tested during PGT SCA1.

Methods. The study material consisted of trophectoderm from 5-6 day-old embryos obtained through an IVF-ICSI cycle from couples in which one spouse had an increased number of CAG repeats in the ATXN1 gene. The research was conducted using nested PCR with detection of the number of trinucleotide repeats in the ATXN1 gene and linked indirect microsatellite markers.

Results. Testing was conducted on 29 embryos from three unrelated families. A haplotype associated with the expansion was identified in 13 embryos. Changes in the number of trinucleotide repeats in the ATXN1 gene were observed in eight embryos.

Conclusion. Changes in the number of CAG repeats in the ATXN1 gene were identified for alleles with expansion: both increases and decreases.

The analysis of frequent pathogenic variants of the GALT gene was carried out over 4.5 years in children with galactosemia, suspected galactosemia, including newborns with elevated or borderline level of total galactose. One prenatal diagnosis case was performed. A total of 36 (33 unrelated) children and 18 parents were examined. In one galactosemia I case, a single homozygous genotype for p.Gln188Arg was identified. Other genotypecases with two identified variants were combinations with the Duarte D2 variant. In 30.3% of cases, one allele remained undetected, in 15.2% – both. The allele frequency was: p.Gln188Arg – 33,9%, p.Lys285Asn – 5,4% and Duarte D2 variant – 41,1%.

For expanded carrier screening (ECS) of pathogenic variants (PV) in genes associated with autosomal recessive diseases (ARD), ACMG proposed an approach that takes into account both the severity of diseases and the carrier frequencies (CF) of PV in genes associated with autosomal recessive diseases. The aim was to assess the CF of PV in genes associated with ARD which are not included in the ACMG recommendations in the Russian population (RP). An assessment of the CF of PV in 303 candidate genes was carried out in a sample of patients of the NMRC TPM (n=1126). Among the genes with the PV frequency exceeding the threshold value of 0.005, genes were selected for the assessment of the PV frequency in the RP, carried out using the «Database of population frequencies of genetic variants of the population of the Russian Federation». Of these, the CF of PV exceeded the threshold value in the SBDS gene (CF=0.01171; p_adj 0,001), associated with the Shwachman–Diamond syndrome, and the ALOX12B gene associated with autosomal recessive congenital ichthyosis (CF=0.005845; p_adj< 0,001). These genes can be considered as candidates for ECS in the RP.

The results of preimplantation genetic testing for aneuploidies (PGT-A) do not always coincide with the true chromosomal constitution of the blastocyst, especially in cases of complex chromosomal rearrangements. This can be explained by truly biological reasons, such as the self-correction of chromosomally abnormal embryos and mosaicism, as well as by PGT-A procedural specificity. In this report, we analyzed the trophectoderm (TE) and the inner cell mass (ICM) cells from one blastocyst using array comparative genomic hybridization (aCGH) and fluorescent in situ hybridization (FISH) methods and compared the obtained results with the result of PGT-A. PGT-A by aCGH revealed tetrasomy of the short arm of chromosome X in the TE cells of the blastocyst advocating for its unsuitability for uterine transfer. A re-biopsy of TE was performed, followed by aCGH, and then the remaining part of the blastocyst was divided into TE and ICM for analysis by FISH with DNA probes for the short arm and pericentromeric region of chromosome X. In each of the 10 examined TE cell nuclei, four signals corresponding to chromosome X were detected, and in each of the 7 examined ICM cell nuclei, two signals were detected. To summarize, in TE, both aCGH and FISH detected tetrasomy for the short arm of chromosome X. In contrast, ICM showed no chromosomal imbalance for the short arms of chromosome X. Thus, true inter-tissue mosaicism for tetrasomy of the short arm of chromosome X was revealed.

Background. Increased extracellular ATP is associated with activation of the NLRP3 inflammasome, production of proinflammatory cytokines and development of inflammation. Ectonucleotidases CD39 and CD73, adenosine receptors located on the surface of some immune cells, participate in the regulation of extracellular ATP levels and the adenosinergic signaling pathway. However, information on the expression level of genes encoding these enzymes (ENTPD1 (CD39), NT5E (CD73)) and adenosine receptors in essential arterial hypertension (EAH) is still scarce.

Objective. Determination of the mRNA level of genes encoding proteins of the purinergic signaling pathway (ENTPD1, NT5E, ADORA2A) and the NLRP3 gene in peripheral blood leukocytes (PBL) of patients with EAH.

Patients and methods. The study involved 16 healthy individuals, 17 patients with EAH (stages I-II) (including 8 people before the prescription of antihypertensive drugs and 9 people taking metoprolol (25 mg/day) or bisoprolol (5-10 mg/day) for more than a year). The relative level of gene transcripts was determined by real-time PCR.

Results. The level of the ENTPD1, NT5E, ADORA2A, NLRP3 gene expression in PBL of patients with EAH was higher than in healthy people (p<0,01). The level of NLRP3 gene expression was closely associated with the relative mRNA content of the ENTPD1, NT5E, ADORA2A genes (respectively, r=0,77; 0,66; 0,72; p<0,01).

Conclusion. The formation of EAH is accompanied by an increase in the ENTPD1, NT5E, ADORA2A, NLRP3 genes expression level, which probably reflects the activation of the purinergic signaling pathway in this disease.

Background. It is of particular importance to study how AZF locus deletions on the Y chromosome impact male fertility, particularly through disruptions in mRNA biogenesis regulated by the coilin protein.

Objective. The study aims to investigate associations between the content and distribution of coilin in spermatogenic cells and the type of AZF locus deletion in azoospermic patients.

Methods. The study was performed on testicular biopsies from 12 azoospermic patients. The AZF locus was analyzed by PCR, and coilin was detected by immunohistochemistry.

Results. Analysis of the AZF locus revealed no deletions in 4 samples, gr/gr deletions in 4 samples, and AZFc or AZFb+c deletions in  4  samples. Coilin was localized in the nuclei of only certain spermatogenic cells. In samples with gr/gr deletions, among spermatogonia A, spermatogonia B, spermatocytes I, and haploid spermatogenic cells, the proportion of coilin-positive cells was significantly higher than in samples without AZF deletions (chi-square test, р<0.025 and р<0.001).).

Conclusion. An increased proportion of coilin-positive cells at any stage of spermatogenesis suggests its role in the pathogenesis of male infertility associated with AZF locus deletions. Elevated coilin levels in spermatogenic cells from biopsies with gr/gr deletions indicate its potential involvement in compensatory mechanisms to sustain spermatogenesis.

Most first-year medical university students who come from different schools and colleges have different basic levels of training in genetics. Thus, in the first year, it is necessary to level off knowledge on this subject among students and expand it, forming the basis for further study of medical genetics in higher courses. In order to improve the quality of teaching genetics in the first year of medical university, a survey of students was conducted after studying the subject. The study revealed that the majority of students have the greatest difficulties with studying the molecular foundations of heredity, namely with the processes of matrix synthesis, the structure of the gene and the stages of gene expression. Despite the difficulties, the vast majority of first-year students note the relevance of this subject and want to continue their studies in it, delving into the study of hereditary human diseases and the basics of their occurrence.

Background. Development of prognostic models of disease development allows identification of variables influencing the risk prediction of disease occurrence or recurrence and use of these multiple risk factors in a systematic, reproducible manner in accordance with evidence-based methods. As an example of one of the problems discussed among surgeons is the reduction of the number of recurrences of anterior abdominal wall hernias, as well as prevention of this disease, which can be achieved by early diagnosis of predisposition using methods of analysis of etiopathogenetic features of this multifactorial disease.

Objective: to analyze risk factors and develop a prognostic model of ventral hernia.

Methods. The study was performed on 579 patients. The study included: correlation analysis, ROC analysis and analysis of the importance of etiologic risk factors using an artificial neural network. Morphological factors were studied in skin biopsy and using skin autofluorescence. PCR analysis of rs3809060 WT1 and rs2009262 EFEMP1 was performed.

Results. Based on the results of the study, 1 genetic (rs2009262 EFEMP1) and two morphological factors of connective tissue changes were included in the prognostic model. Subsequently, using logistic regression, a prognosis was made for the occurrence of a hernia, as well as its recurrence, after which patients underwent various types of hernioplasty.

Conclusion. Thus, this study once again proved the major role of genetic and morphological factors associated with changes in connective tissue, determining the surgeon’s tactics.

Background. X-chromosome abnormalities are one of the common genetic causes of disorders of sex development, physical and sexual development, fertility. X-chromosome mosaicism in female patients can lead to various syndromic gonosomal abnormalities (Turner syndrome, trisomy X, and polysomy X, etc.), while similar karyotypes can occur in different clinical forms, this causes their partial overlap.

Aim: to present a clinical case of complex X-chromosome mosaicism in female patient with recurrent pregnancy loss. A 37-year-old woman applied for a genetic examination with complaints of miscarriage. The patient’s development was age-related. There are 3 natural pregnancies in the anamnesis, the first ended in the birth of a healthy boy, the second and the third were frozen in the early stages.

Methods. Standard cytogenetic study was performed on peripheral blood lymphocytes. Fluorescent in situ hybridization was performed on the nuclei of lymphocyte cells and buccal epithelial cells using centromeric probes for chromosomes 18 and X.

Results. The karyotype of the patient according to the standard cytogenetic study was determined as mos 45,X[29]/47,XXX[8]/46,XX[3]. FISH results shown complex X-chromosome mosaicism in peripheral blood lymphocytes – Х(78%)/ХХХ(10%)/ХХ(12%), and buccal epithelial cells – ХХХ(70%)/Х(7%)/ХХХХ(3%)/ХХ(20%).

Conclusion. Some female patients with complex X chromosome mosaicism may not have develop clinical signs characteristic of syndromic gonosomal abnormalities. Since these patients are at risk of premature ovarian insufficiency, they need a timely solution to the issue of reproduction with preimplantation genetic testing for aneuploidy (PGT-A) and prenatal cytogenetic diagnostics.

Subsidized drug coverage out of federal or regional budget resources is available to patients with 28 rare (orphan) diseases; all such patients are listed in federal registries. An additional drug coverage mechanism for children with rare (orphan) diseases under 19 years of age is the Circle of Good Foundation; children are registered in the Foundation’s informational resource. For patients with rare (orphan) diseases over 19 years of age the inclusion in federal registries and subsidized drug coverage can be arranged under several scenarios. For most patients drug coverage is available only if they have the «disabled» status; such patients are not listed in federal registries of patients with rare (orphan) diseases. According to the analysis of federal and regional publicly guaranteed subsidized drug coverage programs under which drug therapy with orphan drugs for patients with rare (orphan) diseases over 19 years of age can be continued, it has been found that it is necessary to expand public drug coverage guarantees for patients with rare (orphan) diseases over 19 years of age based on their «rare» diagnosis without the need to have a disability.

Regardless of communications about associations between genome/chromosome instability with neurodevelopmental disorders, the corresponding research has not been systematically carried out. Here, 300 blood samples of children with neurodevelopmental diseases (autism, intellectual disability, epilepsy) have been evaluated using cytogenetic analysis and SNP-array. Chromosome instability has been revealed in 25 cases (8.3%), genome insurability has been found in 56 cases (18.7%). Thus, 27% of children with neurodevelopmental diseases demonstrate genomic chaotization mediated by chromosome and genome instability.

Multiple hereditary exostoses (MHE) is a genetic disorder characterized by the formation of benign osteochondromas. Pathogenic variants in the EXT1 and EXT2 genes represent the molecular cause of MHE, although there are cases with unknown etiology. Recent studies suggest that proteins such as FUT7 and PTPN11 could also be involved in the pathogenesis of MHE. In this study, using AlphaFold modeling, we analyzed protein interactions between EXT1, EXT2, their pathogenic variants, FUT7, and PTPN11. We confirmed a robust interaction between EXT1 and EXT2, essential for the formation of the native glycosyltransferase complex; disruption of this interaction might explain pathogenicity of previously described variants. No direct binding sites were detected between EXT1 and FUT7. However, our study revealed potential consensus binding sites between EXT1 and PTPN11, indicating its possible involvement in MHE pathogenesis. Our findings provide insights into the molecular basis of MHE, suggesting further avenues for research and potential therapeutic approaches.

This study reports on the identification of an intragenic deletion encompassing exons 30-32 of the DMD gene, facilitated through chromosomal microarray analysis in a patient presenting with psychomotor delay. The findings enabled the diagnosis of Becker muscular dystrophy at a preclinical stage. The results underscore the efficacy of as a diagnostic tool in the screening of patients exhibiting an undifferentiated phenotype.