Romano-Ward syndrome (RWS), the autosomal dominant form of the congenital long 
QT syndrome, is characterised by prolongation of the cardiac repolarisation 
process associated with ventricular tachyarrhythmias of the torsades de pointes 
type. Genetic studies have identified mutations in six ion channel genes, KCNQ1, 
KCNH2, SCN5A, KCNE1 and KCNE2 and the accessory protein Ankyrin-B gene, to be 
responsible for this disorder. Single-strand conformation polymorphism (SSCP) 
analysis and subsequent DNA sequence analysis have identified a KCNQ1 mutation 
in a family that were clinically conspicuous due to several syncopes and 
prolonged QTc intervals in the ECG. The mutant subunit was expressed and 
functionally characterised in the Xenopus oocyte expression system. A novel 
heterozygous missense mutation with a C to T transition at the first position of 
codon 343 (CCA) of the KCNQ1 gene was identified in three concerned family 
members (QTc intervals: 500, 510 and 530 ms, respectively). As a result, proline 
343 localised within the highly conserved transmembrane segment S6 of the KCNQ1 
channel is replaced by a serine. Co-expression of mutant (KCNQ1-P343S) and 
wild-type (KCNQ1) cRNA in Xenopus oocytes produced potassium currents reduced by 
approximately 92%, while IKs reconstitution experiments with a combination of 
KCNQ1 mutant, wild-type and KCNE1 subunits yielded currents reduced by 
approximately 60%. A novel mutation (P343S) identified in the KCNQ1 subunit gene 
of three members of a RWS family showed a dominant-negative effect on native IKs 
currents leading to prolongation of the heart repolarisation and possibly 
increases the risk of malign arrhythmias with sudden cardiac death.