Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias

• Published in: Nature genetics Vol. 12; no. 1; pp. 17 - 23
• Main Authors: Wang, Q, Curran, M.E, Splawski, I, Burn, T.C, Millholland, J.M, VanRaay, T.J, Shen, J, Timothy, K.W, Vincent, G.M, de Jager, T, Schwartz, P.J, Towbin, J.A, Moss, A.J, Atkinson, D.L, Landes, G.M, Connors, T.D, Keating, M.T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.01.1996
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; Cardiac dysrhythmias; Cardiology. Vascular system; Chromosomes, Human, Pair 11; Cloning, Molecular; Female; Genetic Linkage; Heart; Humans; Long QT Syndrome - genetics; Male; Medical sciences; Molecular Sequence Data; Pedigree; Point Mutation; Polymorphism, Single-Stranded Conformational; Potassium Channels - genetics; Sequence Alignment; Sequence Deletion; Sequence Homology, Amino Acid; Genetic mapping; Heart; Human; Nucleotide sequence; Arrhythmia; Prolonged QT interval; Cardiovascular disease; Ionic channel; Gene expression; Conduction disorder; Chromosome C11; Complementary DNA; Gene; Heart block; Heart disease; Risk factor; Predisposition; Deletion; Genetics; Mutation; Potassium
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng0196-17

Genetic factors contribute to the risk of sudden death from cardiac arrhythmias. Here, positional cloning methods establish KVLQT1 as the chromosome 11-linked LQT1 gene responsible for the most common inherited cardiac arrhythmia. KVLQT1 is strongly expressed in the heart and encodes a protein with structural features of a voltage-gated potassium channel. KVLQT1 mutations are present in affected members of 16 arrhythmia families, including one intragenic deletion and ten different missense mutations. These data define KVLQT1 as a novel cardiac potassium channel gene and show that mutations in this gene cause susceptibility to ventricular tachyarrhythmias and sudden death.