Genetic studies of Long QT syndrome

The QT interval is a representation of the cardiac ventricular repolarization process on the electrocardiogram. QT interval varies as a function of age, sex, heart rate, genetic variation and cardiac and non-cardiac drugs. Some individuals may have "normal" QT intervals, but are more susceptible to cardiac arrhythmias, potentially caused by genetic factors underlying QT variability in the general population. A twin study was conducted in which the genetic and environmental influences on QT and corrected QT interval were compared, based on different adjustment formulae. The current report provided evidence that corrected QT interval heritability estimates depend on the specific correction formula applied, as well as that approximately a quarter of the uncorrected QT interval heritability is due to genes specific to QT interval, while the remainder is shared with genes for heart rate. This thesis also aimed to show the penetrance of mutations occurring in the KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 cardiac ion channel genes in clinically '. , diagnosed Long QT Syndrome (LQTS) cases. This study showed that the overall detection rate for mutations in the five defined LQTS genes was approximately 31%. Interestingly, a KCNH2 protein linked C terminal mutation was found to produce a prematurely truncated KCNH2 channel and protein defective trafficking using functional analysis. Page 3 •