title: A Common Mutation of Long QT Syndrome Type 1 in Japan.
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.
  
  
  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.
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science.
authors.forename: Hideki
authors.initials: H
authors.lastname: Itoh
authors.forename: Kenichi
authors.initials: K
authors.lastname: Dochi
authors.forename: Wataru
authors.initials: W
authors.lastname: Shimizu
authors.forename: Isabelle
authors.initials: I
authors.lastname: Denjoy
authors.forename: Seiko
authors.initials: S
authors.lastname: Ohno
authors.forename: Takeshi
authors.initials: T
authors.lastname: Aiba
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kimura
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.forename: Megumi
authors.initials: M
authors.lastname: Fukuyama
authors.forename: Kanae
authors.initials: K
authors.lastname: Hasagawa
authors.forename: Eric
authors.initials: E
authors.lastname: Schulze-Bahr
authors.forename: Pascale
authors.initials: P
authors.lastname: Guicheney
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D044466:Asian People; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007564:Japan; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008297:Male; D009154:Mutation; D029597:Romano-Ward Syndrome / Q000235:genetics*
chemical_list: D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human