Journal of Molecular Medicine

, Volume 79, Issue 9, pp 504–509

A novel long-QT 5 gene mutation in the C-terminus (V109I) is associated with a mild phenotype

Authors

  • Eric Schulze-Bahr
    • Institute for Arteriosclerosis Research, University of Münster, Molecular Cardiology, Domagkstrasse 3, 48149 Münster
  • Martin Schwarz
    • Institute for Neural Signal Transduction, Center for Molecular Neurobiology Hamburg, University of Hamburg
  • Susanne Hoffmann
    • Institute for Neural Signal Transduction, Center for Molecular Neurobiology Hamburg, University of Hamburg
  • Horst Wedekind
    • Department of Cardiology and Angiology, Hospital of the University of Münster, 48129 Münster
  • Harald Funke
    • Institute for Arteriosclerosis Research, University of Münster, Molecular Cardiology, Domagkstrasse 3, 48149 Münster
  • Wilhelm Haverkamp
    • Institute for Arteriosclerosis Research, University of Münster, Molecular Cardiology, Domagkstrasse 3, 48149 Münster
  • Günter Breithardt
    • Institute for Arteriosclerosis Research, University of Münster, Molecular Cardiology, Domagkstrasse 3, 48149 Münster
  • Olaf Pongs
    • Institute for Neural Signal Transduction, Center for Molecular Neurobiology Hamburg, University of Hamburg
  • Dirk Isbrandt
    • Institute for Neural Signal Transduction, Center for Molecular Neurobiology Hamburg, University of Hamburg
Original Article

DOI: 10.1007/s001090100249

Cite this article as:
Schulze-Bahr, E., Schwarz, M., Hoffmann, S. et al. J Mol Med (2001) 79: 504. doi:10.1007/s001090100249

Abstract

Mutations in the human minK gene KCNE1 have been linked to autosomal dominant and autosomal recessive long-QT (LQT) syndrome, a cardiac condition predisposing to ventricular arrhythmias. minK and KvLQT1, the LQT1 gene product, form a native cardiac K+ channel that regulates the slowly delayed rectifier potassium current IKs. We used single-strand conformation polymorphism and sequencing techniques to identify novel KCNE1 mutations in patients with a congenital LQT syndrome of unknown genetic origin. In 150 unrelated index patients a missense mutation (V109I) was identified that significantly reduced the wild-type IKs current amplitude (by 36%) when coexpressed with KvLQT1 in Xenopus oocytes. Other biophysical properties of the IKs channel were not altered. Since we observed incomplete penetrance (only one of two mutation carriers could be diagnosed by clinical criteria), and the family's history was unremarkable for sudden cardiac death, the 109I allele most likely causes a mild phenotype. This finding may have implications for the occurrence of "acquired" conditions for ventricular arrhythmias and thereby the potential cardiac risk for asymptomatic mutation carriers still remains to be determined.

Long QT syndrome KCNE1 minK Genetics Ventricular tachycardia

Copyright information

© Springer-Verlag 2001