[Clinic and genetic polymorphism of Brugada syndrome in Russian patients, caused by mutation in SCN5A gene].

Brugada syndrome (BrS) is an inherited cardiac arrhythmic disorder, characterized by ST-segment elevation in right precordial leads V1-V2>2 mm, pseudo right bundle branch block (RBBB), T-wave inversion and an increased risk of cardiac sudden death (SCD) due to molymorphic VT. It is estimated to be responsible for 12% of SCD cases and about 20% of deaths in patients with structurally normal hearts in autopsy. Mutations in the SCN5A gene account 15-30% of all cases. Clinical, instrumental and genetic analyses were performed for 25 Russian probands with BrS (19 males and 6 female). Phenotype-genotype correlation was studied in SCN5A-positive and SCN5A-negative patients. Rare genetic variants in SCN5A gene were found in 7 of 21 Russian probands (28%). Two variants affect protein splicing (c.IVS16DS-5A>G and c.IVS24AS+1G>A), three missense mutations (p,Y87C, p.R893H and p.S1787N), one in-frame deletion p.del848l, and one non-sense-mutation p.E553X. All mutations were unique for each family. There were no clinical or instrumental parameters were found to be effective in prediction of SCN5A mutations. The protocols of genetic counceling for SCN5A-positive and SCN5A-negative families were established.

[The clinical variability of and approaches to treatment of life-threatening ventricular arrhythmias caused by SCN5A gene mutations].

The reasons for ventricular arrhythmias are variable enough. In many cases the presence and degree of ventricular arrhythmias cannot be explained satisfactorily by the presence of ischemic of inflammatory myocardial lesion. Now that the development of contemporary arrhythmology is associated with active development of molecular-and-genetic research methods, genetic aspects of the pathogenesis of arrhythmias are understood more clearly. Allelic series of diseases that are manifested by arrhythmias that differ clinically but result from mutations in one and the same gene have been described. This paper presents the results of molecular-and-genetic and clinical analysis of diseases caused by mutations in SCN5A gene, which codes the alpha-subunit of the sodium channel Na(v)1.5. Study of clinical manifestations of verified mutations makes it possible to more fully consider possible ways of the development of cardiac rhythm disorders and use the most optimal methods for their treatment.