Original Article

Journal of Molecular Medicine

, Volume 79, Issue 9, pp 504-509

First online:

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

  • Eric Schulze-BahrAffiliated withInstitute for Arteriosclerosis Research, University of Münster, Molecular Cardiology, Domagkstrasse 3, 48149 Münster
  • , Martin SchwarzAffiliated withInstitute for Neural Signal Transduction, Center for Molecular Neurobiology Hamburg, University of Hamburg
  • , Susanne HoffmannAffiliated withInstitute for Neural Signal Transduction, Center for Molecular Neurobiology Hamburg, University of Hamburg
  • , Horst WedekindAffiliated withDepartment of Cardiology and Angiology, Hospital of the University of Münster, 48129 Münster
  • , Harald FunkeAffiliated withInstitute for Arteriosclerosis Research, University of Münster, Molecular Cardiology, Domagkstrasse 3, 48149 Münster
  • , Wilhelm HaverkampAffiliated withInstitute for Arteriosclerosis Research, University of Münster, Molecular Cardiology, Domagkstrasse 3, 48149 Münster
  • , Günter BreithardtAffiliated withInstitute for Arteriosclerosis Research, University of Münster, Molecular Cardiology, Domagkstrasse 3, 48149 Münster
  • , Olaf PongsAffiliated withInstitute for Neural Signal Transduction, Center for Molecular Neurobiology Hamburg, University of Hamburg
  • , Dirk IsbrandtAffiliated withInstitute for Neural Signal Transduction, Center for Molecular Neurobiology Hamburg, University of Hamburg

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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