Cell
Volume 80, Issue 5, 10 March 1995, Pages 795-803
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Article
A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome

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Abstract

To identify genes involved in cardiac arrhythmia, we investigated patients with long OT syndrome (LOT), an inherited disorder causing sudden death from a ventricular tachyarrhythmia, torsade de pointes. We previously mapped LOT 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 7835-36. 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.

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