A novel mutation associated with Jervell and Lange-Nielsen syndrome in a Japanese family

Seiko Ohno, Tomoyuki Kubota, Hidetada Yoshida, Keiko Tsuji, Takeru Makiyama, Satsuki Yamada, Keisuke Kuga, Iwao Yamaguchi, Tom Kita, Minoru Horie

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Background: The Jervell and Lange-Nielsen (JLN) syndrome is a variant of long QT syndromes (LQTS) and is associated with congenital deafness. The syndrome is caused by homozygous or compound heterozygous mutations in genes KCNQ1 and KCNE1, which are responsible for encoding the delayed rectifier repolarizing current, IKS. Methods and Results: A novel and homozygous KCNQ1 mutation in a 23-year-old deaf woman with a prolonged QT interval and recurrent syncope in a Japanese family was identified. Genetic analyses revealed that the proband harbored a KCNQ1 missense mutation (W248F) located in the intracellular S4-S5 linker on both alleles. The same mutation was identified in both maternal and paternal families in a heterozygous manner. However, the family members of both sides had no clinical evidence of LQTS or hearing defects. Functional assays using a heterologous expression system revealed that W248F KCNQ1 plus KCNE1 channels reconstitute hardly measurable IKS currents. In contrast, heterozygous wild-type/W248F KCNQ1 plus KCNE1 channels displayed biophysical properties similar to those of the wild-type KCNQ1 plus KCNE1 channels with a weak dominant-negative effect. Conclusion: In this study, we present a family with JLN syndrome. The electrophysiological properties of the mutant IKS channels explain the pathophysiology underlying JLNS.

Original languageEnglish (US)
Pages (from-to)687-693
Number of pages7
JournalCirculation Journal
Issue number5
StatePublished - 2008


  • Ion channel
  • Jervell and Lange-Nielsen syndrome
  • KCNQ1
  • Long QT syndromes
  • Molecular screening

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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