Hypokalemia‐Induced Long QT Syndrome with an Underlying Novel Missense Mutation in S4‐S5 Linker of KCNQ1

• DOI: 10.1111/j.1540-8167.2000.tb00178.x
• Publication Date: 2007-04-20T13:10:15Z
• Authors: TOMOYUKI KUBOTA; WATARU SHIMIZU; SHIRO KAMAKURA; MINORU HORIE
• Keywords: Short QT syndrome; Linker

Novel Mutation in Hypokalemia‐Induced LQTS. Congenital long QT syndrome (LQTS) is caused by mutations at least five genes coding for cardiac potassium or sodium channels that regulate the duration of ventricular action potentials. Acquired LQTS often associated with drugs metabolic abnormalities. A 47‐year‐old woman who presented marked prolongation (QTc = 620 msec 1/2 ) and repeated episodes torsades de pointes hypokalemia (2.6 mEq/L) was screened using polymerase chain reaction/single‐strand conformation polymorphism (PCR/SSCP). We identified a novel missense mutation intracellular linker S4‐S5 domains KCNQ1, resulting an amino acid substitution cysteine arginine position 259 (R259C). Whole cell, patch clamp experiments were conducted on COS7 cells transfected wild‐type and/or R259C KCNQ1 without KCNE1. Functional analyses mutant subunit revealed its functional homozygous state, producing significantly smaller current than less severe dominant‐negative effect IKS‐ The KCNQl molecular basis I Ks dysfunction underlying apparently sporadic case hypokalemia‐induced LQTS, consistent mild likely to disclose clinical manifestation context hypokalemia. Our findings suggest gene carriers such might not he so rare as commonly expected patients acquired stress importance mutational analysis detecting either “silent” forms congenital novo mutations.