Many countries are introducing a non-invasive prenatal test, NIPT, into the public health system as a contingent screening for pregnant women, which improves the detection of chromosomal abnormalities of the fetus and reduces the number of unwarranted invasive procedures. Analysis of the literature showed that the majority of doctors and pregnant women from the high and intermediate risk groups are ready to use NIPT as an additional screening due to its safety, high sensitivity and the possibility of early reception of results. However, there were found differences between countries in choosing the method of prenatal screening for chromosomal abnormalities of the fetus, which depend on the ethnic, sociodemographic and religious characteristics of the respondents, as well as on the peculiarities of the local health policy related to the need for partial or full payment of the prenatal test and the availability of abortion. It was concluded that each country needs its own guidelines, developed with taking into account the social context, and the issue of introducing NIPT into routine practice should be decided by the results of sociological research among large groups of pregnant women and healthcare professionals in the country.

Congenital Adrenal Hyperplasia (CAH) - group of diseases based on the defect of the one of the enzymes which are involved in cortisol biosynthesis in the adrenal cortex. CAH is one of the most common inborn errors of metabolism that are transmitted as autosomal-recessive traits, which can be fatal or disabling in the case of the late diagnosis. The aim of this study is the evaluation of the efficacy of the CAH neonatal screening due to 21-hydroxylase deficiency in RNO-Alania, study of the structure and detection of the CAH frequency in the region also molecular-genetic features in the population. Retrospective analysis of medical records of the patients with CAH, diagnosed before the implementation of neonatal screening, was performed and tests results of the newborns, who were tested for CAH for 11 years, from the period January 2007 to December 2017. Studies revealed that 21-hydroxylase deficiency, which is more common in CAH, is 1:18725 among the newborns, which is considerably lower then in general in Russia (1:9500). However, high frequency of rare type of the CAH - 3 β-hydroxysteriod dehydrogenase deficiency was revealed in the ossetian population 1:22 470. In most world populations the 21- hydroxylase deficiency is dominant type and is 100 times higher then 3β-HSD. Taking into consideration that among ossetian ethic group close marriages are rare, high frequency of the detected mutation W230X in 3β-HSD gene can be explained by «founder effect».

Background. Hypertrophic cardiomyopathy (HCM) is a hereditary pathology, the main cause of which is mutations in the genes encoding the protein components of the myofibril apparatus of cardiomyocytes, and the spectrum of these genetic changes has population features. The aim of the study was to determine the spectrum of mutations in the genes encoding sarcomeric proteins in patients with HCM from Belarus, as well as to study the association between the genotype and the phenotypic manifestations of the disease. Materials and methods. The study included 340 unrelated patients with HCM from Belarus. Mutation detection in the coding sequences of ACTC1, MYBPC3, MYH7, MYL2, MYL3, TNNI3, TNNT2, TNNС1 и TPM1 genes was performed by next generation sequencing (NGS) in 89 patients. The directed search for genetic defects detected by the NGS method was carried out by the automatic sequencing method using Sanger and PCR-RFLP analysis. Results. The NGS method allowed to detect mutations in the genes of 51,7% of patients: MYBPC3 (20,2%), MYH7 (16,9%), TPM1 (3,4%), ACTC1 (2,3%), MYL2 (1,1 %) and TNNC1 (1,1%). In 6,7% of individuals two (5,6%) or three (1,1%) substitutions were observed. New mutations were found: p.Ala49Asn, p.Val1407Phe in the MYH7 gene; p.Tyr501Ser, p.Trp1007fs, p.Tyr1043*, p.Pro1066Arg, p.Arg1138fs, p.Pro1181Gln, р.Cys1202Arg in the MYBPC3 gene. The most frequently occurring mutations were identified: p.Gln1233*, p.Ser871Alafs, the combination of the р.Glu1265Val + p.Cys1266Arg, R.Gln401*, and Trp1214Arg in the MYBPC3 gene, p.Glu924Lys and p.Glu1356Lys in the MYH7 gene. According to the ECG study, carriers of mutations in sarcomere protein genes, especially with missense mutations in the MYBPC3 gene, had more severe myocardial hypertrophy and early disease manifestation then patients without mutations in those genes. The p.Gln1233* mutation was the most common among Belarusian patients and characterized by late onset of the disease, mild left ventricular myocardial hypertrophy and the more frequent development of atrial fibrillation. Conclusions. In general, the distribution of mutations in the genes encoding sarcomeric proteins in patients with HCM from Belarus didn’t differ from other European populations. 84,9% of the detected mutations were localized in MYBPC3 and MYH7 genes.

The results of medical genetic study of three Districts of the Republic of North Ossetia-Alania (RNOA) - Ardonsky, Pravoberezhny and Kirovsky, with a total number of 116897 people, are reviewed. A survey of the investigated Districts was conducted totally (regardless of nationality, age and gender structure), in accordance with the Protocol of genetic-epidemiological studies - development of the Research Centre for Medical Genetics. After the segregation analysis, we calculated the load of the main types of Mendelian hereditary pathology (AD, AR and X-linked) for the entire population of three regions of the Republic. Segregation analysis demonstrated good agreement between the observed and expected segregation frequencies for both AR and AD diseases. The load (per 1000 individuals) of Mendelian hereditary pathology (autosomal dominant, autosomal recessive and X-linked) was estimated. In the urban populations the load of autosomal dominant pathology was 3.62 in Ardonsky, 1.86 in Pravoberezhny and 2.10 in Kirovsky District; in the rural populations the load of autosomal dominant pathology was substantially higher: 5.33 (Ardonsky), 3.23 (Pravoberezhny), 4.13 (Kirovsky). The prevalence rates of autosomal recessive disorders in urban populations were per 1.17 in Ardonsky, 1.59 in Pravoberezhny and 2.82 in Kirovsky District. In the rural populations of these Districts they were 1.81 in Ardonsky, 2.38 in Pravoberezhny, 3.10 in Kirovsky District. The values of the load of X-linked pathology varied from 0.43 in the urban population of the Pravoberezhny District to 1.29 in the urban population of the Kirov District. Characteristics of the load of hereditary diseases of the considered Districts of RNOA are close to those that were obtained for the population of some areas of the Republic of the Volga-Ural region and the North Caucasus. In the Russian populations of the European part of Russia the values of load of hereditary pathology are significantly lower.

Ain: to evaluate the associations between working memory parameters and Val158Met (rs4680) polymorphism of the COMT gene in young adults. Methods: 371 young adults of both sexes 25-44 years old were recruited from population sample of Novosibirsk. The study included 199 (53,6%) men (average age was 36,54 ± 5,67 years) and 172 (46,4%) women (average age was 36,84 ± 5,75 years). Cognitive function were determined by standardized screening methods. Luria’s 10-words test, letter cancellation test (modified Bourdon’s test), and test of excluded of incorrect words (verbal version of the test) with fixing the time for its implementation, as well as animal naming test were used. Genomic DNA was isolated from venous blood by the phenol-chloroform extraction. Genotyping of the Val158Met polymorphism (rs4680) of the COMT gene was performed using PCR with RFLP. Results: Statistically significant associations (p < 0,05) between quantity of the animals who are correctly called in 1 minute, with time which was spent for exclution of incorrect words, as well as with the first reproduction of the words memorized immediately in Luria test and Val158Met (rs4680) polymorphism of the COMT gene in young adults were revealed. Moreover the quantity of the complaints about the forgetfulness of used phone numbers had significantly higher in the presence of one or two A alleles of the Val158Met polymorphism of the COMT gene. Conclusion: The allele A of the Val158Met (rs4680) polymorphism of the COMT gene, especially in the homozygous state, has a significant association with the working memory parameters of Novosibirsk residents.

We report 2-year-old girl with two monogenic diseases - adrenogenital syndrome with autosomal recessive inheritance mode and periventricular nodular heterotopia type 7 with autosomal dominant, diagnosed by two different molecular genetic methods. The presence of adreno-genital syndrome diagnosed in the first days of life based on typical clinical manifestations and the homozygous mutation was detected p.R356Wby direct DNA testing CYP21А2 gene. The presence of the second monogenic disease was proposed base on the observation the severe delay of psychomotor and speech development and abnormalities of the brain structure detected by MRI. Clinical exome sequencing identified previously not described single nucleotide substitution c.2015С>T (p.W672I) in NEDD4L gene. Pathogenic variants in HECT domain of this protein lead to periventricular nodular heterotopia type 7 (OMIM:617021). Analysis of segregation this variant in the family by direct sequencing of Sanger showed its origin de novo.