In the framework of genetic-epidemiological studies of the Rostov region in 131 patients with phenylketonuria were analyzed for DNA diagnostics, indicators of the level of phenylalanine and according to clinical manifestations of the disease from the genotype of the patients. In 130 patients with phenylketonuria detected 40 mutations (49 different genotypes) in the gene РАН , one in the gene PTS. The analysis of Geno-phenotypic correlations, studied the relationship between genotypes and indices of phenylalanine before treatment and on a background of spent therapy. During the study, the results obtained suggest that depending on the clinical picture of phenylketonuria from РАН genotype. Regression analysis showed a significant negative correlation between the activity of the enzyme phenylalanine hydroxylase and indicators of the level of phenylalanine in patients with repeated analysis and a result of diet.

Chronic heart failure (CHF) is one of the high-end causes of populations disability and mortality. Considering the fundamental role of neurohormonal systems in CHF development, the current approach is the study of genes, what expression products take part in formation of different types for myocardial remodeling and CHF progression. Three polymorphic loci in ACE gene- rs4343 (2350 G>А) , rs4291 (240A>T), rs4340 (I/D) in 271 patient of CHF (functional class II-IV) with different types of the left ventricle (LV) remodeling and 194 conditionally healthy men and women of corresponding age, also their haplotypes were studied. Homozygous genotypes *G*G locus rs4343 and *D*D locus rs4340 , also haplotype, based on these two loci, *DG gene ACE , are significant for CHF developing and remodeling LV, considering different types. By revising haplotypes for all three polymorphic loci of ACE gene (rs4291 , rs4340 and rs4343 ), the predominance of haplotype *TDG was statistically significant for patients with marked hypertrophy LV and moderate hypertrophy LV.

Skin melanoma - a malignant disease of the person with a high risk of metastasis. In countries with a predominantly white population of melanoma among the top ten most socially important categories of tumors, both in terms of morbidity and mortality. Estimation of some morphological characteristics of tumors is essential in determining the prognosis of the disease and the formation of high-risk groups in patients with melanoma. The aim of this study was to determine the association between the mutational status of BRAF gene, and clinical and morphological features of the skin melanoma patients of the South of Russia. Molecular genetic study of exon 15 of BRAF performed direct sequencing method of Sanger and by RT-PCR in 100 patients with a Russian South morphologically confirmed diagnosis of skin melanoma. It is found that the presence of mutations in the BRAF gene was significantly associated with an increased level of infestation by Clark. Also, there was a statistically significant increase in the frequency of tumor ulceration by 54% in patients with the presence of activating mutations V600. It has been found that tumors with activating mutations in the BRAF gene were more frequent in areas of skin exposed to periodic solar insolation (trunk). Tumors without mutations in the BRAF gene prevailed on the areas of skin with chronic sun exposure (head and neck). The overall frequency of somatic symptoms V600 mutations in the BRAF gene was 57% (57 of 100 patients). In this study the gene in BRAF have been identified mutations three options with different frequencies of occurrence: p.V600E (88%), p.V600K (10%) and K601> E (2%). In patients younger than 50 years, the frequency of occurrence V600 mutations was significantly higher than in the group of patients older than 50. Also, for patients younger than 50 years has been characterized by the absence of mutations V600K and a higher incidence of V600E mutation (1.7 times).

The identification of somatic mutations has the potential to offer diagnostic and prognostic information and inform the selection of therapies. The present study is focusing on implementation of clinical exome sequencing using a Trusight one sequencing panel targeted 4,813 genes associated with known clinical phenotypes. Paired-ended sequencing was performed in six gastric cancer samples and six corresponding adjacent normal gastric specimens using Trusight one sequencing panel on a NEXTSEQ500 platform. We found 102 somatic mutations, all of them were SNP, 30 of them were synonymous substitutions, 66 were nonsynonymous substitutions and six were nonsense mutations. We found 82 novel mutations, from them 10 mutations were localized in genes previously associated with gastric cancer pathogenesis. Somatic mutation of established clinical utility was identified for one patient, and predictively driver mutations were found for three patients. Strategies to effectively and responsibly use these diverse results are required to incorporate tumor exome sequencing and other NGS tests into clinical practice.

Background. Mutations in the ABCA4 gene cause Stargardt disease and other blinding autosomal recessive retinal disorders. However, sequencing of the complete coding sequence in patients with clinical features of Stargardt disease sometimes fails to detect both mutations required to cause the disease. It has previously been hypothesized that mutations near rare alternate splice junctions in ABCA4 might cause disease by increasing the probability of mis-splicing at these sites. Deep next-generation sequencing of RNA extracted from human donor eyes revealed 15 alternate exons that are weakly expressed in normal human retina. Cryptic intronic splice sites, activation of which by mutations might lead to the formation of ABCA4 disease causing alleles, have been identified. Objective. To analyze the cryptic splice sites in the noncoding regions of the ABCA4 gene in Russian patients with Stargardt disease. Material and methods. High throughput parallel semiconductor sequencing of all previously described minor exons was performed on peripheral blood cells DNA from 29 patients with Stargardt disease. Results. In the group of patients under study we have identified only genetic variants in the cryptic splice sites that represent common polymorphisms and that cannot thus be interpreted as disease causing mutations. Our cohort of the patients lacked apparently disease causing intronic nucleotide substitutions that were previously identified in the North American and European populations. Conclusion. Failure to identify ABCA4 intronic mutations in this study may be explained by low representation of patients with one or no exonic mutations in our cohort and does not compromise the utility of intron cryptic splice sites sequencing as a part of Stargardt disease molecular genetic diagnostics.

Importance . Congenital malformations are the main cause of disability in infancy. Aniridia (OMIM #106210) is a severe autosomal dominant congenital disorder. Aniridia is mainly associated with pathogenic variants in the PAX6 gene. Objective . To investigate the mutational and clinical spectra of congenital aniridia in a cohort of Russian patients. To make a design of a protocol for diagnosis of congenital aniridia. Design, Setting and Participants. 34 patients with congenital aniridia from 27 unrelated families were analysed. DNA-diagnosis included sequencing of all coding exons of PAX6 gene as well as analysis of large 11p13 region deletions. Results . 22 sporadic and 12 familial cases of congenital aniridia patients underwent detailed ophthalmic examination and molecular diagnosis. Large 11p13 deletion affecting PAX6 and WT1 genes was identified in two patients, therefore they were diagnosed with WAGR syndrome. Molecular analysis involved Sanger sequencing of all PAX6 exons, as well as Multiplex Ligation-dependent Probe Amplification (MLPA), Loss Of Heterozygosity (LOH) assays and FISH analysis. Small intragenic mutations in PAX6 gene were identified in 23 patients including 7 novel and 8 different previously reported changes. Large deletions were found in the remaining 11 patients. This allowed designing the protocol for congenital aniridia diagnosis. Conclusions and Relevance . Mutation detection rate is 100% in the current study. The protocol for diagnosis of congenital aniridia was designed on the basis of genetic peculiarities in Russian aniridia patients.

We report on a rare case of interstitial deletion in the short arm of chromosome 4 including the segment p15.1-p15.32 and not including the critical region of Wolf-Hirschhorn syndrome. Size and location of this deletion were specified by metaphase CGH. Special aspects of phenotypic appearance of this syndrome are discussed.