A Common Mutation of Long QT Syndrome Type 1 in Japan

• Published in: Circulation Journal 2015/08/25, Vol.79(9), pp.2026-2030
• Main Authors: Itoh, Hideki, Dochi, Kenichi, Shimizu, Wataru, Denjoy, Isabelle, Ohno, Seiko, Aiba, Takeshi, Kimura, Hiromi, Kato, Koichi, Fukuyama, Megumi, Hasagawa, Kanae, Schulze-Bahr, Eric, Guicheney, Pascale, Horie, Minoru
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age of Onset; Asian Continental Ancestry Group; Child; Child, Preschool; Female; Humans; Japan; KCNQ1; KCNQ1 Potassium Channel - genetics; Long QT syndrome; Male; Mutation; Mutations; Romano-Ward Syndrome - genetics
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.CJ-15-0342

Background:Previous studies of long QT syndrome (LQTS) have revealed the presence of country-specific hot spots inKCNQ1mutations, 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. (Circ J 2015; 79: 2026–2030)