Multiple mutations in associated with LQTS genes in patients with life-threating ventricular tachyarrhythmias

Long QT syndrome (LQTS) is the genetically determined disease characterized by the QT interval elongation at the electrocardiogram, a high risk of life-threatening arrhythmias and sudden cardiac death. This syndrome is determined by mutations in genes encoding ion channel proteins, as well as proteins indirectly associated with ion channels. 4.5-8% of patients with LQTS have more than one mutation in the genes associated with the development of channelopathies. Purpose of work: description of two clinical cases of patients with life-threatening arrhythmia in which a combination of rare mutant alleles in the genes associated with LQTS was detected. The clinical examination included 12-lead ECG, echocardiography, cardiac MRI with delayed contrast, and 24-hour ECG monitoring (SM ECG). Genetic testing was performed by next generation sequencing (NGS) using the TruSight ™ Cardio Sequencing Panel reagent kit (Illumina). Both patients with no burdened family history had malignant ventricular tachyarrhythmias, which required the implantation of a cardioverter defibrillator. The NGS method allowed to detect a combination of substitutions in the genes ANK2 (c.9161C>G, p.Ala3054Gly, rs139007578) and KCNE1 (c.253G>A, p.Asp85Asn, rs1805128) in a patient with idiopathic ventricular tachycardia. In the patient with idiopathic ventricular fibrillation, the allelic variant was also found in the gene ANK2 (c.1397C>T, p.Thr466Met, rs786205722) and an additional substitution in the gene SNTA1 (c.1877>T, (p.Ala263Ser), rs150576530). If patients have several genetic defects, a “cumulative effect” of mutations can be observed, phenotypically manifested by a severe course of the disease with unfavorable outcomes. It has been shown that when genotyping patients with idiopathic life-threatening tachyarrhythmias, the use of panels with a large number of genes associated with cardiovascular pathology is quite justified. A comprehensive study of genes can increase the diagnostic and prognostic value of genetic screening.

long QT syndrome, multiple mutations, next generation sequencing (NGS), phenotypic manifestations

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