The mutation L69P in the PAS domain of the hERG potassium channel results in LQTS by trafficking deficiency.

ABSTRACT: The congenital long QT syndrome (LQTS) is a cardiac disorder characterized by a prolonged QT interval on the electrocardiogram and an increased susceptibility to ventricular arrhythmias and sudden cardiac death. A frequent cause for LQTS is mutations in the KCNH2 gene (also known as the human ether-a-go-go-related gene or hERG), which reduce or modulate the potassium current I_Kr and hence alter cardiac repolarization. In a patient with a clinically diagnosed LQTS, we identified the mutation L69P in the N-terminal PAS (Per-Arnt-Sim) domain of hERG. Functional expression in HEK293 cells shows that a homotetrameric hERG channel reconstituted with only mutant subunits exhibits a drastically reduced surface expression of the channel protein thus leading to a dimi

SUBMITTER: Jenewein T 

PROVIDER: S-EPMC7188350 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature