Long QT syndrome with compound mutations is associated with a more severe phenotype: A Japanese multicenter study

Hideki Itoh, Wataru Shimizu, Kenshi Hayashi, Kenichiro Yamagata, Tomoko Sakaguchi, Seiko Ohno, Takeru Makiyama, Masaharu Akao, Tomohiko Ai, Takashi Noda, Aya Miyazaki, Yoshihiro Miyamoto, Masakazu Yamagishi, Shiro Kamakura, Minoru Horie

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Background: Long QT syndrome (LQTS) can be caused by mutations in the cardiac ion channels. Compound mutations occur at a frequency of 4% to 11% among genotyped LQTS cases. Objective: The purpose of this study was to determine the clinical characteristics and manner of onset of cardiac events in Japanese patients with LQTS and compound mutations. Methods: Six hundred three genotyped LQTS patients (310 probands and 293 family members) were divided into two groups: those with a single mutation (n = 568) and those with two mutations (n = 35). Clinical phenotypes were compared between the two groups. Results: Of 310 genotyped probands, 26 (8.4%) had two mutations in the same or different LQTS-related genes (compound mutations). Among the 603 LQTS patients, compound mutation carriers had significantly longer QTc interval (510 ± 56 ms vs 478± 53 ms, P = .001) and younger age at onset of cardiac events (10 ± 8 years vs 18 ± 16 years, P = .043) than did single mutation carriers. The incidence rate of cardiac events before age 40 years and use of beta-blocker therapy among compound mutation carriers also were different than in single mutation carriers. Subgroup analysis showed more cardiac events in LQTS type 1 (LQT1) and type 2 (LQT2) compound mutations compared to single LQT1 and LQT2 mutations. Conclusion: Compound mutation carriers are associated with a more severe phenotype than single mutation carriers.

Original languageEnglish (US)
Pages (from-to)1411-1418
Number of pages8
JournalHeart Rhythm
Volume7
Issue number10
DOIs
StatePublished - Oct 2010

Keywords

  • Compound
  • Gene
  • Long QT syndrome
  • Mutation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Long QT syndrome with compound mutations is associated with a more severe phenotype: A Japanese multicenter study'. Together they form a unique fingerprint.

  • Cite this

    Itoh, H., Shimizu, W., Hayashi, K., Yamagata, K., Sakaguchi, T., Ohno, S., Makiyama, T., Akao, M., Ai, T., Noda, T., Miyazaki, A., Miyamoto, Y., Yamagishi, M., Kamakura, S., & Horie, M. (2010). Long QT syndrome with compound mutations is associated with a more severe phenotype: A Japanese multicenter study. Heart Rhythm, 7(10), 1411-1418. https://doi.org/10.1016/j.hrthm.2010.06.013