Novel KCNQ1 mutations associated with recessive and dominant congenital long QT syndromes: evidence for variable hearing phenotype associated with R518X

Hum Mutat. 2000 Apr;15(4):387-8. doi: 10.1002/(SICI)1098-1004(200004)15:4<387::AID-HUMU26>3.0.CO;2-T.

Abstract

Congenital long QT syndrome may be transmitted as either an autosomal dominant or recessive trait. Two families with the autosomal recessive Jervell and Lange-Nielsen syndrome (JLNS), and one family with the autosomal dominant Romano-Ward syndrome (RWS) were evaluated for mutations in KCNQ1. Two different novel frameshift mutations were discovered in one of the JLNS families (1188delC) and in the RWS family (504delG). A third allele (R518X) was observed in the second JLNS family. The R518X allele was previously associated with recessive long QT syndrome without deafness, but was present in a congenitally deaf proband in our study. These data extend the range of known KCNQ1 mutations associated with both recessive and dominant forms of congenital long QT syndrome, and demonstrate that the R518X allele may be associated with or without congenital deafness.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Child, Preschool
  • Female
  • Frameshift Mutation / genetics*
  • Genes, Dominant / genetics*
  • Genes, Recessive / genetics*
  • Hearing / genetics*
  • Humans
  • KCNQ Potassium Channels
  • KCNQ1 Potassium Channel
  • Long QT Syndrome / congenital*
  • Long QT Syndrome / genetics*
  • Male
  • Mutation, Missense / genetics
  • Pedigree
  • Phenotype
  • Potassium Channels / genetics*
  • Potassium Channels, Voltage-Gated*

Substances

  • KCNQ Potassium Channels
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Potassium Channels
  • Potassium Channels, Voltage-Gated