Association between clinical and genetic diagnosis in patients with LQT syndrome: importance of genetic testing

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

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigacion Clínica (SAIC); 2019

SAIC-SAFE-SAB-SAP 2019

Long QT syndrome (LQTS) is a congenital genetic disorder that cause lethal cardiac arrhythmia and sudden death (SD). About 15 genes encoding ionic channels have been implicated. The most frequent are those encoding for the K+ channels KCNQ1 (40-45%) and HERG (40-45%), and the Na+ channel Nav1.5 (5-8%). Dysfunction in these channels leads to lengthening of the QT interval in ECG. Molecular identification of the causes of this disease contributes to better diagnosis, risk stratification and to improve pharmacological treatments. For that reason, our aim is to correlate clinical diagnosis with genetic variants of LQTS. We examined the LQT-associated genes KCNQ1 (LQT1), KCNH2 (LQT2) and SCN5A (LQT3) using gDNA extracted from 6 subjects. 5 of them showed a prolonged QT interval on the ECG (>460 ms) while 1 first-degree relative presented a normal QT interval (A (p.Ser546=) in 2 subjects. In 1 patient we could not amplify exon 16, 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 variant c.982C>T (p.Arg328Cys). For SCN5A no variants were found at the tested exons.We found benign and pathological genetic variants in either KCNQ1 or KCNH2 genes of our population. No information about the exon 16 deletion for KCNQ1 as a pathological variant has been reported. To the best of our knowledge, this is the first genetic testing of LQTS performed in Argentina. Knowledge of genetic status will impact in patient life quality since they can know their risk for arrhythmia and will allow to modify their habits.