To identify genes involved in cardiac arrhythmia, we investigated pati
ents with long QT syndrome (LQT), an inherited disorder causing sudden
death from a ventricular tachyarrhythmia, torsade de pointes. We prev
iously mapped LQT loci on chromosomes 11 (LQT1), 7(LQT2), and 3(LQT3).
Here, linkage and physical mapping place LQT2 and a putative potassiu
m channel gene, HERG, on chromosome 7q35-36. Single strand conformatio
n polymorphism and DNA sequence analyses reveal HERG mutations in six
LQT families, including two intragenic deletions, one splice-donor mut
ation, and three missense mutations. In one kindred, the mutation aros
e de novo. Northern blot analyses show that HERG is strongly expressed
in the heart. These data indicate that HERG is LQT2 and suggest a lik
ely cellular mechanism for torsade de pointes.