A Common Mutation of Long QT Syndrome Type 1 in Japan

Circ J. 2015;79(9):2026-30. doi: 10.1253/circj.CJ-15-0342. Epub 2015 Jun 29.

Abstract

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Asian Continental Ancestry Group
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Japan
  • KCNQ1 Potassium Channel / genetics*
  • Male
  • Mutation*
  • Romano-Ward Syndrome / genetics*

Substances

  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human