title: A novel mutation associated with Jervell and Lange-Nielsen syndrome in a Japanese family.
abstract: 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, I(Ks).
  
  
  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 I(Ks) 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.
  
  
  CONCLUSIONS
  In this study, we present a family with JLN syndrome. The electrophysiological properties of the mutant I(Ks) channels explain the pathophysiology underlying JLNS.
authors.affiliation: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Ohno
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kubota
authors.forename: Hidetada
authors.initials: H
authors.lastname: Yoshida
authors.forename: Keiko
authors.initials: K
authors.lastname: Tsuji
authors.forename: Takeru
authors.initials: T
authors.lastname: Makiyama
authors.forename: Satsuki
authors.initials: S
authors.lastname: Yamada
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kuga
authors.forename: Iwao
authors.initials: I
authors.lastname: Yamaguchi
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
mesh_terms: D000328:Adult; D000818:Animals; D044466:Asian People / Q000235:genetics*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003638:Deafness / Q000235:genetics; D005192:Family Health; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D029593:Jervell-Lange Nielsen Syndrome / Q000235:genetics* / Q000503:physiopathology; D051657:KCNQ1 Potassium Channel / Q000235:genetics* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D020125:Mutation, Missense; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics* / Q000502:physiology
chemical_list: C489622:KCNE1 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D024642:Potassium Channels, Voltage-Gated