Several mutations in the human ether-a-go-go-related K+ channel gene (HERG or KCNH2) cause long QT syndrome (LQT2) by reducing the intracellular transport (trafficking) of the channel protein to the cell surface.
An exercise stress test was performed in 23 patients with a pore region mutation and in 22 patients with a C-terminal end mutation of the cardiac potassium channel gene causing LQT1 type of long QT syndrome (KVLQT1 gene), as well as in 20 patients with mutations of the cardiac potassium channel gene causing LQT2 type of long QT syndrome (HERG gene) and in 33 healthy relatives.
Mutations in KCNH2 (the gene that encodes hERG1) causes LQT2, one of the most common forms of long QT syndrome, a disorder of cardiac repolarization that predisposes affected subjects to ventricular arrhythmia and increases the risk of sudden cardiac death.
In a family with long QT syndrome (LQT2), some individuals who did not harbor the HERG mutation had a prolonged QTU interval on electrocardiograms after exercise.
A novel mutation in human ether-a-go-go-related gene, alanine to proline at position 490, found in a large family with autosomal dominant long QT syndrome.
Rescue of aberrant gating by a genetically encoded PAS (Per-Arnt-Sim) domain in several long QT syndrome mutant human ether-á-go-go-related gene potassium channels.
We therefore analysed variations in the LQTS-associated genes KCNQ1 (LQT1) and KCNH2 (LQT2) using cardiac blood and myocardial tissue from subjects having died suddenly during MP or NPS use to investigate the relationship between congenital genetic abnormalities and sudden death during illegal drug use.
One SCN5A and four KCNH2 mutations (38%) were identified in 13 definite LQTS families, one SCN5A mutation (20%) in five Brugada syndrome families and one (25%) PKP2 (plakophyllin2) mutation in four ARVC families.
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.