Gastric cancer is a malignant tumor of the human gastric mucosa, characterized by high metastatic potential and poor prognosis. This disease is multifactorial and is based on a hereditary predisposition. The study of the molecular genetic basis of malignant tumors of the stomach is a prerequisite for the development of new approaches to its diagnosis and the appointment of optimal therapy. This review describes the current state of knowledge about gastric cancer, and also describes the latest achievements in the field of molecular genetics of this disease.

Niemann-pick disease type C is a rare autosomal recessive neurodegenerative disorder, the real incidence of which has been underestimated because of not specific clinical symptoms. The clinical symptoms of NP-C are highly variable with different onset terms of manifestations from fetal and neonatal period to adulthood. In recent years there has been a growing use of biomarkers as a selective screening and panel genetic tests which contributed to the earlier detection of the disease in patients. The article contains the most important clinical manifestations and their combinations, as well as an update to the existing recommendations for clinical practice.

The most common WD causing in the patients from Europe is p.H1069Q mutation. The results of study of p.H1069Q mutation in Russian patients and control group by using developed test-system are presented in this investigation. Querying the chromosomal haplotype of Russian patients with p.H1069Q mutation by two micro satellite markers showed a general haplotype which is suggestive of the founder’s effect.

Background. Metabolic syndrome (MS) with atrial fibrillation (AF) is a significant medical and social problem. AF is a multifactorial disease with a genetic predisposition. Aldosterone contributes to the myocardial fibrosis and remodeling. So, investigation of influence of the aldosterone synthase CYP11B2 gene variants on serum aldosterone level and the risk of AF in patients with MS is of great interest. The purpose of the study was to assess serum aldosterone level as well as the frequency of cases of AF among MS patients with different С(-344)T variants of the CYP11B2 gene (rs1799998). Materials and methods. 201 MS patients (including 99 subjects with AF) and 267 controls were recruited to the study. All participants underwent serum aldosterone level measurement and С(-344)T variants detection with PCR followed by restriction analysis. Results. The frequency of TT genotype in controls was lower than in the MS whole group (p = 0.013) and lower than in the «MS without AF» group (p = 0.005). TT genotype was associated with increased risk of MS [OR = 2,00 (95%CI 1,23-3,26)] as well as with increased risk of «MS without AF» [OR = 1,66 (95%CI 1,11-2,48)]. Aldosterone level in the MS whole group was greater than in controls (p<0.001), and in the «MS with AF» group aldosterone level was greater than in the «MS without AF» group (p = 0.029). In controls, the T allele carriers showed greater aldosterone level compared to the CC genotype carriers (p = 0.015). Conclusion. We showed the association of (-344) Т allele of the aldosterone synthase CYP11B2 gene with the risk of MS, but not with the risk of AF.

The results of multiplex ligation-dependent probe amplification in molecular-genetic diagnosis of Marfan syndrome are reported.

Congenital aniridia (OMIM #106210) (ВА) is a Mendelian autosomal dominant panocular disorder with complete penetrance and variable expressivity. The incidence of aniridia is 1 in 45,000-100,000 births. Aniridia is characterized by congenital absence of the iris with foveal hypoplasia and other eye abnormalities. The most cases of aniridia is caused by heterozygous mutations in the PAX6 gene or chromosome 11p13 rearrangements. Molecular analysis (including Sanger sequencing as well as MLPA analysis and the loss of heterozygosity analysis) of 110 patients referred with congenital aniridia from 84 unrelated families identifies causative PAX6 mutations in all except 3 patients (81/84). A significant proportion of point PAX6 mutations affecting canonical splicing sites and deeper intronic sequences (13,6%) (11 different mutations in 18 patients) have been revealed. Intron sequence variants pathogenic status is established in accordance with ACMG recommendations for interpretation of sequence variants. The manuscript gives consideration to the functional evidence of a revealed in patient with congenital aniridia VUS (variant of unknown clinical significance) NG_008679.1(PAX6_v001):c.142-14C>G effect on the splicing pattern. We used a minigene system to determine the effect of investigated mutation in vitro in human cell line HEK293. Our analysis has shown that this single nucleotide substitution leads to a splicing disruption due to the use of the new acceptor-site of intron 5. That leads to exon 6 elongation by 13 nucleotides, open reading frame shifting (NM_000280.4(PAX6_v001):c.141_142insTTCCCCTATGCAG, p.Val48PhefsTer12) and aberrant mRNA degradation by NMD (nonsense-mediated mRNA decay) mechanism. Thus, the intron sequence variant produces a null allele, leading to a haploinsufficiency of the PAX6 -function and the development of disease.

The targeted NGS was used to search for mutations, associated with hypertrophic cardiomyopathy in a 28-year-old patient. TruSight Cardiomyopathy Sequencing panel allowed to detect c.864 + 3_864 + 6delGAGT deletion (rs397516751) that affects a natural splice site in intron 6 in the LAMP2 gene. The LAMP2 (lysosomal-associated membrane protein 2, Xq24) codes for a membrane glycoprotein necessary for lysosome adhesion and autophagy. Mutations in this gene are associated with Danon disease, which can manifest as a phenocopy of hypertrophic cardiomyopathy. The NGS made it possible to correct the diagnosis. Data of other clinical cases are presented in the article, confirming the pathogenicity of mutations that affect the donor splice site in intron 6 in the LAMP2 .