Genetics, molecular mechanisms and management of long QT syndrome

Qing Wang, Qiuyun Chen, Jeffrey Towbin

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Cardiac arrhythmias cause more than 300,000 sudden deaths each year in the USA alone. Long QT syndrome (LQT) is a cardiac disorder that causes sudden death from ventricular tachyarrhythmias, specifically torsade de pointes. Four LQT genes have been identified: KVLQT1 (LQT1) on chromosome 11p15.5, HERG (LQT2) on chromosome 7q35-36, SCN5A (LQT3) on chromosome 3p21-24, and MinK (LQT5) on chromosome 21q22. SCN5A encodes the cardiac sodium channel, and LQT-causing mutations in SCN5A lead to the generation of a late phase of inactivation-resistant whole-cell inward currents. Mexiletine, a sodium channel blocker, is effective in shortening the QT interval corrected for heart rate (QTc) of patients with SCN5A mutations. HERG encodes the cardiac I(Kr) potassium channel. Mutations in HERG act by a dominant-negative mechanism or by a loss-of-function mechanism. Raising the serum potassium concentration can increase outward HERG potassium current and is effective in shortening the QTc of patients with HERG mutations. KVLQT1 is a cardiac potassium channel protein that interacts with another small potassium channel MinK to form the cardiac I(Ks) potassium channel. Like HERG mutations, mutations in KVLQT1 and MinK can act by a dominant-negative mechanism or a loss-of-function mechanism. An effective treatment for LQT patients with KVLQT1 or MinK mutations is expected to be developed based on the functional characterization of the I(Ks) potassium channel. Genetic testing is now available for some patients with LQT.

Original languageEnglish (US)
Pages (from-to)58-65
Number of pages8
JournalAnnals of Medicine
Volume30
Issue number1
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

Fingerprint

Long QT Syndrome
Molecular Biology
Potassium Channels
Mink
Mutation
Chromosomes
Sudden Death
Potassium
Sodium Channel Blockers
Mexiletine
Torsades de Pointes
Sodium Channels
Genetic Testing
Tachycardia
Cardiac Arrhythmias
Cause of Death
Heart Rate
Serum
Genes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Genetics, molecular mechanisms and management of long QT syndrome. / Wang, Qing; Chen, Qiuyun; Towbin, Jeffrey.

In: Annals of Medicine, Vol. 30, No. 1, 01.01.1998, p. 58-65.

Research output: Contribution to journalArticle

Wang, Qing ; Chen, Qiuyun ; Towbin, Jeffrey. / Genetics, molecular mechanisms and management of long QT syndrome. In: Annals of Medicine. 1998 ; Vol. 30, No. 1. pp. 58-65.
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