Background. Lysosomal acid lipase deficiency (LALD) is a continuum of autosomal recessive diseases caused by defects in the enzyme of lipid metabolism, lysosomal acid lipase (LAL). LAL encodes by the gene LIPA. The most common variant of LIPA c.894G>A caused the disease in more than а half of cases. The true frequency of LALD is unknown. In Russia it is supposed to be 1:150000 - 1:100000 of newborns. The aim of the work is the selective biochemical screening for LALD, the study of LIPA mutation spectrum and the estimation of the LALD incidence in Moscow. Materials and methods. 1999 рatients suspected of lysosomal storage diseases (LSD) took part in the study. Dried blood spots of 920 newborns of Moscow were obtained for the estimation of c.894G>A allelic frequency. LAL activity was measured by fluorometric analysis. The LIPA gene was studied by direct sequencing and RFLP-analysis. Results and discussion. In 34 cases diagnosis of LALD was confirmed. Totally, 16 different variants of LIPA were found, 11 variants were novel. Ten of the novel variants were classified as pathogenic, one was uncertain significance. The allele c.894G>A was the most common LIPA variant in the cohort of patients, so as in many Europe populations. The allelic frequency of the variant in the newborns collection was estimated as 1:270 and LALD frequence was 1:73.159. Conclusion. Screening for LALD is a useful tool for diagnostics among LSD suspected patients. The allelic frequency of the variant c.894G>A seems the same as in European populations. In comparison with this data, there are many rare and novel variants in the Russian cohort.

Blepharophimosis-Ptosis-Epicanthus inversus syndrome (BPES) is a disease characterized by malformations of the eyelids: ptosis, blepharophimosis and the presence of a reverse epicant or telecant (BPES). This syndrome in women can be accompanied by a premature ovarian exhaustion syndrome and related infertility. This work summarizes the results of FOXL2 gene analysis for 24 patients from 19 unrelated families with an incoming diagnosis. Mutations were detected in 10 unrelated families

Background. In hereditary retinoblastoma, a germline mutation in one of the alleles of the RB1 gene causes a predisposition to the disease and its transmission within the pedigree. Hereditary retinoblastoma manifests at an earlier age compared with the sporadic form and in most cases is multifocal and bilateral. However, some families with retinoblastoma (two or more carriers of the same germline mutation in the pedigree) exhibit a milder phenotype with incomplete penetrance (some carriers of the germline mutation are asymptomatic) and variable expressivity (the same mutation in different family members may manifest as either a unilateral or bilateral form). Identification of low-penetrant mutations in the RB1 gene and studying their inheritance in pedigrees contributes to understanding the mechanisms underlying the development of retinoblastoma with low penetrance. It is extremely important both for further expansion of knowledge in the field of molecular genetics of retinoblastoma, and for competent genetic counseling and subsequent clinical management of families with this form of the disease. Objective. To establish the spectrum of genetic disorders in the RB1 gene in Russian patients with hereditary retinoblastoma with incomplete penetrance and variable expressivity and to determine the effect of the parental origin of the RB1 mutation on its phenotypic manifestation. Methods. Using high-performance parallel sequencing, a molecular genetic survey of 332 unrelated patients with retinoblastoma was performed. Sanger sequencing was used to verify the identified point mutations and analyze their segregation in pedigrees. Results. In the group of patients without a family history of retinoblastoma, in 3.5% the hereditary nature of the disease was determined, where one of the parents was an asymptomatic carrier of a germline mutation in the RB1 gene. Ten low-penetrant mutations in the RB1 gene were identified. In 91.7% of cases of hereditary retinoblastoma with low penetrance, the mutant allele was obtained by a proband from a father with no clinical signs of the disease or with a milder form. Conclusion. The results confirm the previously suggested assumptions that low-penetrant germline mutations in the RB1 gene inherited from the father more often lead to the development of retinoblastoma, and in a more severe form than those inherited from the mother.

The study of the phenomenon of longevity is the most promising in populations with a fairly large proportion of centenarians. Since old times cases of pronounced active longevity have been widely known in the Caucasus region. The complexity of age-related processes of aging assumes the involvement of multiple complex factors that have affect on life expectancy. Therefore the study of the pleiotropic genes with their multiple effects and functions could be helpful in that case. The angiotensin I-converting enzyme (ACE) gene and the multiple drug resistance gene ( ABCC11) are of great interest because of their high importance for essential vital functions. The aim of the study was the search for correlations in the frequencies distribution of polymorphic variants of pleoitropic genes ABCC11 and ACE in the population of Abkhazians with the longevity. The material included the DNA samples from indigenous residents of Abkhazia. They were divided into two groups: older age (N = 79) and control (N = 97). The differences in the frequencies distribution of 538G>A genotypes and alleles of the gene ABCC11 in the older group and control were not significant. ACE gene insertion-deletion polymorphism ( rs1799752) genotyping was performed by PCR-AFLP. The genotype frequencies were : II = 0.186; ID = 0.412; DD = 0.402, allele frequencies I and D were equal to 0.392 and 0.608 for the control group of Abkhazians. The older group did not differ significantly from the control in genotype frequencies, the ratio for II/ID/DD genotypes were as 0.088/0.380/0.532, and the frequencies of alleles I and D corresponded to 0.278 and 0.722. The obtained results revealed that the ACE gene deletion allele frequency was significantly increased in the older group of Abkhazians.

Impairments of redox homeostasis play a key role in the development of type 2 diabetes mellitus (T2D). The main endogenous source of the superoxide radical is NADPH oxidase, one of the subunits of which is the light chain of cytochrome b-245, CYBA. The aim of the study was to study the associations of cytochrome b-245 alpha chain gene polymorphisms rs7195830 (G>A), rs8854 (C>T), rs9932581 (C>T) and rs4673 (G>A) with a risk of developing T2D. The study included 1022 patients with T2D (average age 61,1 ± 7,2 years) and 1064 sex-and age-matched healthy volunteers. Genotyping of CYBA gene polymorphisms was performed using iPLEX technology on a MassArray Analyzer 4 genome time-of-flight mass spectrometer (Agena Bioscience). The CYBA gene A/A genotype (rs4673, G>A) was associated with an increased risk of developing the disease (OR 1,49, 95%CI 1,11-1,99, P=0,0074, recessive model). The identified association remained significant even after the adjustment for gender, age, and body mass index (ORadj 1,51, 95%CI 1,09-2,09, padj=0,014). Gender-stratified analysis revealed that the established association rs4673 was characteristic only for females (ORadj 1,60, 95% CIadj 1,04-2,46, padj= 0,032). Patients with T2D had a significantly higher level of hydrogen peroxide in blood plasma compared with the control group (p<0,05), regardless of gender, however, the relationship between the A/A genotype rs4673 with the increase in the content of Н2О2 in plasma by 0,77 mmol/L (p = 0,044) was found only in males. The T/T genotype rs9932581 was associated with an increase in glycated hemoglobin level of 2,71% (p = 0,042) in the general group of patients with T2D, as well as with an increase in the same indicator by 4,44% (p = 0,03) among females. The association of the C/T genotype rs9932581 with an increase in the proportion of HbA1c by 0,61% (p = 0,018) and with an increase in blood glucose level by 1,06 mmol/L (p = 0,029) was noted exclusively in males. The association of fasting blood glucose level was also established with genotype A/A rs7195830, in which carriers the glucose concentration was 1.17 mmol/L higher than in homozygotes for the reference allele (P = 0,022).