OBJECTIVES: We took advantage of the genetic isolate of Finns to characterize a 
common long QT syndrome (LQTS) mutation, and to estimate the prevalence of LQTS.
BACKGROUND: The LQTS is caused by mutations in different ion channel genes, 
which vary in their molecular nature from family to family.
METHODS: The potassium channel gene KCNQ1 was sequenced in two unrelated Finnish 
patients with Jervell and Lange-Nielsen syndrome (JLNS), followed by genotyping 
of 114 LQTS probands and their available family members. The functional 
properties of the mutation were studied using a whole-cell patch-damp technique.
RESULTS: We identified a novel missense mutation (G589D or KCNQ1-Fin) in the 
C-terminus of the KCNQ1 subunit. The voltage threshold of activation for the 
KCNQ1-Fin channel was markedly increased compared to the wild-type channel. This 
mutation was present in homozygous form in two siblings with JLNS, and in 
heterozygous form in 34 of 114 probands with Romano-Ward syndrome (RWS) and 282 
family members. The mean (+/- SD) rate-corrected QT intervals of the 
heterozygous subjects (n = 316) and noncarriers (n = 423) were 460 +/- 40 ms and 
410 +/- 20 ms (p < 0.001), respectively.
CONCLUSIONS: A single missense mutation of the KCNQ1 gene accounts for 30% of 
Finnish cases with LQTS, and it may be associated with both the RWS and JLNS 
phenotypes of the syndrome. The relative enrichment of this mutation most likely 
represents a founder gene effect. These circumstances provide an excellent 
opportunity to examine how genetic and nongenetic factors modify the LQTS 
phenotype.