Long QT Syndrome-Related Antibody Explorer Kit

Long QT syndrome is a congenital arrhythmogenic disorder that may lead to life endangering ventricular arrhythmia, syncope and sudden cardiac death. Patients suffering from Long QT syndrome exhibit prolonged QTc interval during cardiac myocytes action potential. There are various genes that are involved in the pathophysiology of this syndrome¹.

The KCNQ1 gene consists of 16 exons and spans approximately 400 kb. It encodes a cardiac potassium channel that was the first to be discovered as related to the Long QT syndrome. The channel is comprised of an α-subunit with a conserved potassium selective pore signature flanked by six transmembrane segments. The channel requires the α-subunit to assemble with a β-subunit called minK to function properly. In several KCNQ1 mutations, the subunits do not assemble properly resulting in reduced or no potassium current thus leading to prolonged QTc interval². Another gene involved in the syndrome is the KCNH2 gene which also encodes a cardiac myocyte potassium channel. Most mutations in this gene result in a trafficking defect, preventing the channel from reaching the cell surface. However, a newly discovered missense mutation in this gene produces a defect in channel biophysical activity suggesting that other pathophysiological mechanisms also exist³. The sodium channel encoding gene SCN5A has also been found to be involved in Long QT syndrome. The initial mutation discovered includes an intragenetic deletion on 9 nucleotides in a region important for channel inactivation. Unlike potassium channel mutations the SCN5A mutation is a “gain of function” mutation whereas the former are “loss of function” mutations⁴.