A novel long-QT 5 gene mutation in the C-terminus (V1091) is associated with a mild phenotype

Mutations in the human minK gene KCNE1 have been linked to autosomal domina nt and autosomal recessive long-QT (LQT) syndrome, a cardiac condition pred isposing to ventricular arrhythmias. minK and K(v)LQT1, the LQT1 gene produ ct, form a native cardiac K+ channel that regulates the slowly delayed rect ifier potassium current I-Ks. We used single-strand conformation polymorphi sm 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 significantl y reduced the wild-type IKs, current amplitude (by 36%) when coexpressed wi th K(v)LQT1 in Xenopus oocytes. Other biophysical properties of the IKs, ch annel were not altered. Since we observed incomplete penetrance (only one o f two mutation carriers could be diagnosed by clinical criteria), and the f amily'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 th ereby the potential cardiac risk for asymptomatic mutation carriers still r emains to be determined.