The review summarizes current information on the impact of FMF and its treatment on pregnancy outcomes, and analyses the hypothetical teratogenicity of colchicine. In the case of colchicine resistance/intolerability, the possibility of using other drugs during pregnancy, including genetically engineered biological drugs, among which interleukin 1 inhibitors are preferred for FMF. An evolutionary view is presented on the need for amniocentesis in FMF patients receiving colchicine during conception and pregnancy, as well as in cases where colchicine therapy was performed to husbands during conception with their wives. Emphasis is placed on the safety aspects of therapy, the main provisions of which are presented in the clinical recommendations for the treatment of FMF of the European Anti-Rheumatic League (EULAR, 2016). According to these recommendations, colchicine should not be discontinued during conception, pregnancy or lactation; today’s evidence does not support amniocentesis.

The article summarizes the world experience in helping patients with rare diseases, the history of the development of “orphan” medicine, reviews foreign strategies and the fundamental documents that form the modern foreign models of care for patients with orphan diseases. The problems of providing medical care to this group of patients in the Russian Federation are highlighted, including in the framework of the programs “14 high-cost nosologies” and “17 nosologies” (17 life-threatening chronic progressive rare (orphan) diseases). The difficulties associated with the operation of the existing system of medical care for orphan patients are highlighted, including data on assessing the lack of information on management and on the procedure for providing information about patients with rare nosologies to the appropriate structures in the medical environment. The work also analyzes regional Russian and foreign screening programs, a review of relevant diagnostic methods and the experience of their implementation and use. The authors also address issues related to biotechnological innovations in Russian and foreign medicine, emphasizing the relevance, effectiveness and, in some cases, the indispensability of gene therapy. In conclusion, the authors summarize the most significant issues and challenges facing orphan medicine in the Russian Federation, as well as make suggestions for their solution.

Imbalance in secretion of adipose tissue adipokines may play a role in the development of cardiovascular pathology associated with obesity. Omentin-1 is an adipokine with antiinflammatory, antioxidant and antiatherogenic properties, therefore it’s serum concentration is considered as a biomarker of cardiovascular diseases. Objective: Investigation of omentin-1 gene (ITLN1) expression in SAT in coronary artery disease (CAD) patients and in the control group, including сomparative analysis of ITLN1 mRNA and protein levels in SAT, omentin-1 serum concentration, as well as an assessment of the correlation of the ITLN1 gene expression with the mRNA level of PPARG gene encoding peroxisome proliferator-activated receptor gamma as the key regulator of adipogenesis. Subcutaneous adipose tissue (SAT) biopsies and serum samples from 74 patients with CAD, undergoing coronary artery bypass grafting, and 16 persons of the control group, were included in the study. ITLN1 and PPARG mRNA levels were detected by quantitative real-time PCR. Omentin-1 protein level in SAT was measured by western-blot. Serum omentin-1 concentration was determined by ELISA. Serum omentin-1 concentration was decreased in the CAD group compared to controls (p<0,01), and inversely correlated with waist circumference among all examined individuals (r = -0.307, p <0.01). No differences were found in the ITLN1 mRNA and omentin-1 protein levels in SAT between the studied groups. The ITLN1 mRNA and omentin-1 protein levels in SAT were positively correlated (r=0,373, p<0.05). A higher level of omentin-1 protein in SAT was detected in men compared with women (p <0.05), however, omentin-1 serum concentration was higher in women (p <0.05). The PPARG mRNA level in SAT was lower in patients with CAD (p <0.05). Omentin-1 serum concentration was positively correlated with the PPARG mRNA level in SAT (r =0.338, p <0.05). The ITLN1 mRNA and omentin-1 protein levels were negatively correlated with the PPARG mRNA in SAT among all examined individuals (r = -0.444, p <0.01 and r = -0.475, p <0.01, respectively). These correlations persisted only in men subgroup when men and women were analyzed separately (r= -0,422, p<0,05 and r= -0,609, p<0,01, respectively). CAD, adiposity and male gender are associated with reduced omentin-1 serum concentration. Gender differences of omentin-1 gene expression regulation in SAT were demonstrated.

Addictive disorders are multifactorial diseases with clinical, genetic and neurophysiological heterogeneity and high comorbidity with other disorders of the mental spectrum. The decisive influence on the phenotypic dispersion of disorders of behavior of a dependent nature belongs to the genotype. Polymorphic variants of genes of the neurotransmitter systems of the brain that encode proteins involved in the regulation of effector reactions and the metabolism of psychoactive substances can be considered as markers of behavioral patterns and an individual predisposition to dependent behavior. Genotyping by TaqIA polymorphism at the ANKK1/DRD2 locus (rs1800497) and VNTR polymorphism in the SLC6A3 gene (DAT1) was performed using the PCR. A statistically significant predominance of the frequency of the ANKK1*A1 allele and the ANKK1*A1A2 genotype was revealed in the group of men with the presence of addictive disorder in the form of alcohol dependence compared to phenotypically healthy representatives of the control group (p <0.001). The frequency of *A2 and genotype *A2A2 were statistically significantly lower in the study group than in the control. The ANKK1*A1 allele is a risk factor for the development of alcohol dependence (RR=4.69; EF=0.15) with a moderate linkage (j=0.21), and ANKK1*A2 has a protective property (RR=0.84; PF=0.79). The data obtained indicate the possibility of using genotyping of the genes of the dopaminergic system of the brain to assess an individual predisposition to alcohol dependence - in carriers of *A1 of the DRD2/ANKK1 gene, the risk of dependence formation is 4.69 higher than homozygotes in the *A2 variant.

The study aim was to identify ethical problems arising in the process of genetic counseling while using modern methods of genetic testing (WGS, extended carrier screening). A special questionnaire was developed to assess the ethical dilemmas and attitudes of doctors working in the field of medical genetics. The questionnaire consists of 28 complex questions and contains a general part that allows you to evaluate the socio-demographic and professional characteristics of the doctor. The survey was attended by 30 specialists. For doctors it was important to help married couples have healthy children while prescribing genetic tests. The majority of the respondents believed that before marriage, responsible people should know if they or their partners are carriers of mutations that lead to inherited diseases that can be passed on to children. Also, most of the respondents agreed with the need for mandatory screening for the carriage of mutations in the most common monogenic diseases and neonatal screening for Duchenne muscular dystrophy and spinal muscular atrophy. In addition, experts support the creation of an ethical codex for geneticists. In this pilot study, the main vectors of ethical problems of medical and genetic specialists were identified, which require in-depth study in subsequent larger studies.

The long arm of the Y chromosome microdeletions are common genetic cause of male infertility, related with azoospermia and oligozoospermia. The frequency of various Y-chromosome microdeletions can vary significantly in different ethnic groups and have certain features. The aim of the presented research is to determine the frequency and spectrum of AZF (azoospermia factor) microdeletions in infertile men of Armenian nationality, in order to optimize diagnostic and therapeutic measures using assisted reproductive technologies.

With the use of new nanocompounds, in particular, derivatives of fullerene C60, the likelihood of human contact with them increases. It has been shown that water-soluble derivatives of fullerene can affect the transcriptional activity of genes in human embryonic fibroblasts of the lungs (PLEC). Activation of the transcription factor NFkB (nuclear factor kappa-light-chain-enhancer of activated B cells) induces processes aimed at cell survival, as well as the development of a pro-inflammatory response. The expression of genes that provide protection against stress at the cellular level is triggered by a transcription factor, NRF2 (nuclear factor [erythroid-derived 2] -like factor 2). The interaction between NFkB and NRF2 is mainly antagonistic. The search for new compounds that selectively activate the transcription factor NFkB and NRF2 remains an urgent task of modern medicine.

Prolonged exposure to increased of radon doses provokes the accumulation of acyl hydroperoxis in the adolescents blood. The folate cycle gene polymorphism associations with lipid peroxidation intensity have been established.

Pre-examination single cell validation was performed for preimplantation genetic testing (PGT-M) for 9 monogenic disorders by nested PCR for STR and pathogenic variants. Totally 109 single cells and 24 WGA products (by MDA) were analyzed.

The use of high-throughput sequencing in prenatal diagnostics has significantly increased the detection of the causes of fetal abnormalities identified by ultrasound. Establishing a relevant option is important for making a diagnosis and evaluating the prognosis. The purpose of this work is to determine the prevalence and structure of monogenic diseases that cause fetal malformations using next generation sequencing (NGS). In our study, we analyzed 60 samples of fetal DNA whose abnormalities were detected by ultrasound during pregnancy. Pathogenic variants were found in 71% of fetuses.

The results of analyzes the effectiveness of prenatal diagnostics for identifying the fetal chromosomal pathology in the medical-genetic consultation of Kursk.

In this research first applied evolutionary approach to study of the PE genetics architecture via the regulatory polymorphic variants (rSNPs) of differentially expressed genes (DEG), identified by analysis of the transcriptome in placental tissue. The results demonstrate а significant role of 10 rSNP 8 DEG and their adaptive changes at the macroevolutionary and/or microevolutionary level in the formation of hereditary predisposition to PE in Russians and Yakuts.

The problem of prevention and early diagnosis of preeclampsia continues to be one of the leading in obstetrics. It`s a major problem that contributes substantially to maternal and perinatal morbidity and mortality worldwide . Gene expression contributes significantly to the pathogenesis of placental diseases. Traditional methods of studying gene expression are based on the search of differentially expressed genes in a disease, but this approach considers genes in isolation. Coexpression analysis describes the genes involved in the unified biological pathways of the pathological process and also allows you to select in each of the clusters the most functionally significant gene in the network - the hub gene.

It is shown that the key pathogenetic mechanisms of grate obstetric syndromes (GOS) are associated with impaired placentation. The aim of the work was to search for new genetic markers of GOS on the basis of integrative analysis of genome-wide expression profiling data. We found that the transcriptional activity of 64 genes changes in at least two GOS diseases. The significant role of disturbance of intercellular interactions and regulation of protein modification in placental tissue during the development of the pregnancy complications is shown. Master regulators that are potential therapeutic targets have been identified.

In the search for genetic risk factors for preeclampsia, the role of polymorphic variants of key genes of the renin-angiotensin system, pro-oxidant-antioxidant system, and vascular endothelial growth factor was studied, possibly forming its main clinical manifestations: increased blood pressure, placental oxidative stress, and endothelial vascular dysfunction in the «mother-placenta-fetus» circulatory system. Reliable genetic predictors of this pregnancy complication have been determined.

It was found that disturbances of embryonic development are accompanied by multi-locus imprinting disturbance (MLID), the frequency of which is increased in placental tissues of spontaneous abortions from women with recurrent pregnancy loss. It is shown that MLID are accompanied by NLRP7 gene mutations in spontaneous abortions from women with recurrent pregnancy loss, and parents are heterozygous carriers of these mutations.

Skewed inactivation of the X chromosome is characteristic for women with recurrent pregnancy loss and spontaneous abortions with a karyotype 46,XX. Skewed X-inactivation in spontaneous abortion is more often associated with the asymmetric inactivation in the mother.

The first time made conducted study to determine the possible etiological condition of idiopathic forms of recurrent miscarriage by impaired immune interaction of maternal cells with syncytiotrophoblast, as well as by carriage of adverse risk alleles of the main HLA histocompatibility complex class 2.

Kazakh population compares with populations of Europe and Asia by the immune system genes occupies in intermediate position. Frequency distribution analysis of the studied genotypes in the Kazakh population showed their correspondence to Hardy-Weinberg equilibrium (p> 0.05). Due to the high frequency of idiopathic form of recurrent miscarriage (iRM) in human populations, its contribution to reproduction rates, studied immune system genes polymorphisms can be considered as possible genetic factors for the development of this pathology; conduct further research to determine their significance in the development of iRM in Kazakh population.

Estimation of genetic factors that lead to risk of thromboembolic complications in pregnant women, has a great importance in current time. Investigation of gene polymorphisms of hemostatic system (F5 (G1691А), F2 (G20210A), SERPINC1(G786A), PROC(A2583T)) with application of real time polymerase chain reaction in 63 patients with aggravated obstetric anamnesis was done. It was shown that the presence in the genotype of 48 patients (76%) of one or a combination of several low-functional alleles of the studied genes is a risk factor for the development of thrombophilic pregnancy complications (fetoplacental insufficiency, threatening miscarriage, preeclampsia, premature detachment of normally situated placenta, intrauterine fetal death).

Helsmoortel-van der Aa syndrome (OMIM # 615873) is an autosomal dominant mental retardation 28 type, which is characterized by dysmorphic craniofacial features, impaired behavior and autism spectrum disorders. The development of a rare syndrome is associated with mutations in the ADNP gene. The clinical case is presented in patient with a development delay (psychomotor and speech), characteristic facial dysmorphia, impaired behavior and a detected mutation in the ADNP gene. Previously undescribed variant of the nucleotide sequence in the ADNP gene (p.Ala1017fs) was detected by targeted exome sequencing. Heterozygous mutations in the ADNP gene have been described in patients with Helsmoortel-van der Aa syndrome (MIM: # 615873). Mutations in the ADNP gene can be a genetic cause of autism spectrum disorders in 0,17% of patients. It is advisable to take into account that the ADNP gene is one of the key genes for embryonic neurodevelopment when interpreting NGS data in patients with epileptic encephalopathy, autism spectrum disorder and characteristic facial dysmorphia.