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

ME Curran, I Splawski, KW Timothy, GM Vincen… - Cell, 1995 - Elsevier
ME Curran, I Splawski, KW Timothy, GM Vincen, ED Green, MT Keating
Cell, 1995Elsevier
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 …
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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