Genetic Study in Argentinian Patients with Clinical Long QT Syndrome Diagnosis

Author(s): Leonardo Dionisio*, Sofía Stupniki, Eugenio Aztiria, Ezequiel Rías, Leandro Dye, Leonardo Onetto, Franco Gregorietti, Roberto Keegan, Guillermo Spitzmaul

Long QT Syndrome (LQTS) is a genetic cardiac condition in which varying degrees of severity and treatment response. Three are primarily affected by mutations that cause cardiac ion channel dysfunction. In Argentina, most of the LQTS diagnoses are made by clinical examination and ECG analysis. In this study, we evaluated a group of individuals to correlate their clinical diagnosis of LQTS with genetic variations.

Using gDNA isolation, PCR, and exome sequencing, we screened the coding sequences of the KCNQ1, KCNH2, and SCN5A genes. We identified several changes in these genes, most of them previously described in the literature, but also a novel variation. We found an alteration in the sequence of KCNQ1 exon 16 which did not allow us to amplify it. This is the first analysis of genetic variations in LQTS in Argentina conducted by a national research laboratory. The combination of the detected variations may explain the prolongation of the QT interval observed in the ECG of some of the individuals and may help to improve the treatment making it more rational as well as provide genetic counselling to first-degree relatives.