A Common Mutation of Long QT Syndrome Type 1 in Japan

Background: Previous studies of long QT syndrome (LQTS) have revealed the presence of country-specific hot spots in KCNQ1 mutations, and the purpose of this study was to evaluate the influence of a common mutation on clinical phenotypes in Japanese LQT1 patients. Methods and Results: We retrospectively studied the frequency of each mutation in 190 LQT1 Japanese probands and evaluated the clinical severity of LQT1 among carriers with a common mutation. We also compared it with that of carriers with other mutations. In the Japanese cohort, the most common mutation was p. A344spl (c.1032 G> A), comprising a substitution of a guanine for an adenine at the last base of exon 7, and it was found in 17 probands (8.9%). Regarding the clinical characteristics of A344spl carriers, the mean age-of-onset was 10+/-4 years, > 40% were symptomatic, and the mean corrected QT interval was 461+/-30 ms. The prognosis for carriers of the A344spl mutation (n= 31) was intermediate between that for the A341V mutation reported to be associated with severe phenotypes (n= 24) and other mutations (n= 290). Conclusions: The A344spl mutation was a frequent LQTS genotype in Japan, which indicates that the influence of country-specific hot spots should be considered when studying LQT1 clinical phenotypes.