FIRST REPORT OF GENETIC VARIANTS DETECTED IN ARGENTINIAN PATIENTS WITH CLINICAL LQT SYNDROME DIAGNOSIS

DIONISIO, L.; AZTIRIA, E.; STUPNIKI, S.; DYE, L.; ONETTO, L.; GREGORIETTI, F.; KEEGAN, R.; SPITZMAUL, G.

Buenos Aires

Congreso; 16th World Congress of Arrhythmias; 2019

Sociedad Argentina de Electrofisiología Cardíaca (SADEC)

Introduction: Long QT syndrome (LQTS) is a congenital genetic disorder that can cause lethal cardiac arrhythmia and sudden death(SD). About 15 genes encoding ionic channels or associated proteins have been implicated. The most frequent are those encoding forthe slow rectifying K+ channel KCNQ1 (40-45%), the fast rectifying K+ channel HERG (40-45%), and the fast Na+ channel Nav1.5 (5-8%). Dysfunction of one or more of these channels leads to lengthening of the QT interval in ECG. Molecular identification of thecauses of this disease contributes to better diagnosis, risk stratification and treatment of this group of patients.Objectives: Our aim was to correlate clinical diagnosis with genetic variants of LQTS.Methods: We examined the LQT-associated genes KCNQ1 (LQT1), KCNH2 (LQT2) and SCN5A (LQT3) using gDNA extractedfrom 6 subjects. 5 of them showed a prolonged QT interval on the ECG (>460 ms) while 1 first-degree relative presented a normalQT interval (A (p.Ser546=) in 2 subjects. In 1 patient we could not amplify exon16, suggesting an exon deletion. For KCNH2, we found the following variants: c.1692A>G (p.Leu564=) in 1 patient, c.1956T>C(p.Tyr652=) in most of the cases (5/6) and c.2690A>C (p.Lys897Thr) in 1 patient. Finally, we found the likely-pathogenic variantc.982C>T (p.Arg328Cys). For SCN5A no variant were found in the few exons that were sequenced so far.Conclusion: We concluded that several benign genetic variants were detected in our population but in 2 patients pathologicalchanges in either KCNQ1 or KCNH2 genes were detected. No information about the deletion of exon 16 for KCNQ1 as a pathologicalvariant has been reported. To the best of our knowledge, this is the first genetic testing of LQTS performed in Argentina. This studyrepresents a kick-start for a systematic survey of the Argentinian population, characterized by its heterogeneous genetic background.