To study the role of genetic factors in personality traits development and possible association with the hormonal status of an individual, it is relevant to analyze the polymorphism of genes affecting mental processes, in particular, the arginine-vasopressin receptor gene (AVPR1A). The aim of this study was to search for associations of the microsatellite locus RS1, which affects f AVPR1A expression level, with the hormones level of the anterior lobe of the pituitary gland and personality traits in the Yakut population. The study sample included Yakut men aged 18-26 years (n=121). Analysis of the number of RS1 repeats was carried out using PCR method and sequencing of the primary nucleotide sequence. Serum hormone levels were determined by enzyme-linked immunosorbent assay (ELISA). In the Yakut population alleles and genotypes frequencies of the AVPR1A RS1 locus have been determined, “short” (S) alleles containing ≤10 repeats (63%) and the corresponding SS genotypes (44.6%) were more frequent, while individuals with “long” (LL) and “heterozygous” (SL) genotypes accounted for 18.2% and 37.2%, respectively. To search for a possible association between the AVPR1A RS1 locus and the hormonal status of Yakut men, we analyzed associations between the SS, SL, and LL genotypes and the level of hormones of the anterior lobe of the pituitary gland such as ACTH, TSH, FSH, and LH. The range of concentrations of ACTH and TSH in the group of individuals with SS genotypes was significantly lower than that observed in the group of LL genotype-carriers (p=0.042 and p=0.048, respectively), and the LH level, on the contrary, was statistically significantly higher (p=0.029). When searching for associations between genotypes of the RS1 AVPR1A locus and individual variance in personality traits, it was found that individuals with SS genotypes demonstrated statistically significant increase in such personality traits as “novelty seeking” (p=0.02) and “reward dependence ” (p=0.01) compared to LL genotypes. The results obtained indicate the modulating effect of genetic variants of the AVPR1A gene in the formation of interindividual differences in the level of hormones of the anterior lobe of the pituitary gland, which could affect the manifestation of psychoemotional sphere in humans.

Background. Dependent behavior disorders are multifactorial diseases with high heterogeneity and comorbidity. The etiopathogenetic mechanisms of behavioral disorders of the addictive spectrum, with all the breadth of the study, have not been studied enough. Comprehensive genetic studies of addictive pathology using clinical genealogical and molecular genetic methods of research are of interest both scientifically and from a practical point of view, since they contribute to a deep study of the sample and increase the effectiveness of using the data obtained in medical genetic counseling. Aim: to study the genetic component of addictive behavior in the form of alcohol dependence. Methods. The study included 181 probands from two comparison groups: men with alcohol dependence (F10.212; F10.222; n=120) and phenotypically healthy men in the control group (n=61). The clinical and genealogical characteristics of the examined men were studied; a comparative analysis of pedigrees was carried out, taking into account relatives of I, II degrees and both degrees of relationship (n=5068). Genotyping by TaqIA polymorphism at the ANKK1/DRD2 locus (rs1800497) and VNTR polymorphism in the SLC6A3 gene (DAT1) was performed using the PCR. Results. An analysis of the frequency and distribution of alcohol dependence among relatives of I, II and both degrees of relationship of men dependent on alcohol and phenotypically healthy men revealed a high frequency of alcohol dependence with a predominant lesion of males in the pedigrees of men with alcoholism (p<0.001). The frequency of alcohol dependence among the fathers and brothers of addicted probands is 72.5% and 58%, respectively. A statistically significant predominance of the frequency of the ANKK1*A1 allele was revealed in the group of men with the presence of addictive disorder in the form of alcohol dependence compared to the control group (p<0.001). Conclusions. The hereditary burden of alcoholism in the pedigrees of men with alcoholism indicates the presence of a genetic component in the pathogenesis of alcohol dependence and indicates the genetic basis of alcohol dependence as a chemical form of addictive behavior. Carrying the ANKK1*A1 allele seems to be a risk factor for the development of an addictive disorder in the form of alcohol dependence, and ANKK1*A2 has a protective property in this respect.

Pathogenic variants in the GJB2 gene are the most common molecular cause of nonsyndromic autosomal recessive sensorineural hearing loss type 1 (DFNB1). The aim of the work was to evaluate the spectrum of genetic variants and the proportion of GJB2-associated hearing loss in patients with hereditary non-syndromic hearing disorders in the Ossetian population from the Republic of North Ossetia-Alania. Sanger sequencing of 1 and 2 exons of the GJB2 gene, followed by analysis of the variation in the number of copies of loci by multiplex ligase-dependent amplification (MLPA) was carried out. The study was conducted on a sample of 83 patients with hereditary nonsyndromic sensorineural hearing loss from 74 unrelated families from the population of Ossetians of the Republic of North Ossetia-Alania (RSO-Alania). The cause of nonsyndromic sensorineural hearing loss in Ossetians in the RSO-Alania, due to pathogenic variants of the GJB2 gene, was confirmed in 26.8% of patients. Two genetic variants (GJB2(NM_004004.6):c.358_360del (p.Glu120del)) - 54.2% и GJB2(NM_004004.6):c.35del (p.Gly12ValfsTer2) - 37.5%) account for 91.7% of pathogenic alleles of the GJB2 gene in Ossetian patients.

Recent advances in sequencing technologies have enabled identification of multiple genes associated with intellectual disability disorders, including QRICH1 gene. Ververi-Brady syndrome (VBS; MIM: #617982) is a rare developmental disorder, characterized by mild developmental delay, mildly impaired intellectual development and speech delay and mild dysmorphic facial features. For the first time in Russia, clinical and molecular description of two patients with epilepsy, developmental and speech delay, and mild dysmorphic facial features is presented. The variants nucleotide sequence in QRICH1 gene - missense mutation (c.1711G>A; p. Asp571Asn) and frameshift mutations (c.1963_1964insT; p.Lys655IlefsTer) were detected by whole exome sequencing. To date, thirty-eight individuals have been reported with QRICH1 mutations in the world.

We report two DSD patients’ cases associated with unique mosaicism and psu dic(Y;22). The first patient has four cell lines in karyotype: mos 47,XYY[9]/46,XY,psu dic(Y;22)(p11.32;p13)dn[9]/45,X[3]/46,ХY[9]. The second patient has two abnormal cell lines in karyotype: mos 45,X[16]/45,X.ish psu dic(Y;22)(q11;p13)dn [9]. In both patients the psu dic(Y;22) was formed de novo, gonosomal mosaicism was detected in peripheral blood lymphocytes and buccal epithelium. The inter-tissue variability of different cell lines was estimated as high (patient 1) and extremely high (patient 2). We discuss clinical phenotypes, suppose mechanisms of sex chromosome abnormalities and mosaicism formation, diagnostic problems and result nuances.