title: Genetics, molecular mechanisms and management of long QT syndrome.
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.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston 77030, USA. qwang@bcm.tmc.edu
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.forename: J A
authors.initials: JA
authors.lastname: Towbin
mesh_terms: D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002891:Chromosomes, Human, Pair 21; D002893:Chromosomes, Human, Pair 3; D002897:Chromosomes, Human, Pair 7; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D005799:Genes, Dominant; D005808:Genes, Recessive; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D015221:Potassium Channels / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics
chemical_list: D015221:Potassium Channels; D015222:Sodium Channels