Title: A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.

Authors: M E Curran, I Splawski, K W Timothy, G M Vincent, E D Green, M T Keating

Journal, date & volume: Cell, 1995 Mar 10 , 80, 795-803

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/7889573

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