This study substantiates a causal link between quinidine and QT interval prolongation in SQT1 and suggests that quinidine may be a potential pharmacological agent for treating SQT1 patients.
Our findings show that both drugs demonstrate efficacy in reversing the SQT1 phenotype, and indicate that disopyramide warrants further investigation as an alternative to quinidine in the treatment of SQT1.
These are the first data to visually demonstrate mutation-specific differences in the trafficking-deficient LQT2 phenotype, and this study has identified a novel way to categorize trafficking-deficient LQT2 mutations based on differences in intracellular retention.
Enhancement of HERG protein expression through Hsp90 inhibition of CHIP binding might be a novel therapeutic strategy for long QT syndrome 2 caused by trafficking abnormalities of HERG proteins.
Defective functional PM expression of the human ether-a-go-go-related gene (hERG) K(+) channel leads to the prolongation of the ventricular action potential that causes long QT syndrome 2 (LQT2), with increased propensity for arrhythmia and sudden cardiac arrest.
Loss-of-function KCNH2 mutations cause the type 2 long QT syndrome (LQT2), and most LQT2-linked missense mutations inhibit the trafficking of Kv11.1 channels.
Identification and functional characterization of the novel human ether-a-go-go-related gene (hERG) R744P mutant associated with hereditary long QT syndrome 2.
We designed multivariate logistic models to predict the presence of the KCNH2 mutation or moxifloxacin while adjusting for the level of QTc prolongation and the level of heart rate in LQT2 patients.
The risk for life-threatening cardiac events from birth through age 40 years (comprising aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) was assessed among 1,166 LQT2 male (n = 490) and female (n = 676) patients by the location of the LQTS-causing mutation in the KCNH2 channel (prespecified in the primary analysis as pore-loop vs. non-pore-loop).
Our results suggest that a rare polymorphism KCNE1-D85N underlies the development of an LQT2 phenotype in this young athlete by interacting with KCNH2 to cause a dominant-negative effect to reduce I(Kr).
Of these, zebrafish models have involved targeting two different KCNH2 gene (long QT syndrome 2) orthologues, termed zerg-2 and zerg-3, with differing cardiac phenotypes.
Type 2 congenital long QT syndrome (LQT2) results from KCNH2 or hERG gene mutations. hERG encodes the K(v)11.1 alpha subunit of the rapidly activating delayed rectifier K(+) current in the heart.
Type 2 congenital long QT syndrome (LQT-2) is linked to mutations in the human ether a-go-go-related gene (HERG) and is characterized by rate-corrected QT interval (QTc) prolongation, ventricular arrhythmias, syncope, and sudden death.