Identification of an ethnic-specific variant (V207M) of the KCNQ1 cardiac potassium channel gene in sudden unexplained death and implications from a knock-in mouse model

Int J Legal Med. 2009 May;123(3):253-7. doi: 10.1007/s00414-009-0321-3. Epub 2009 Feb 7.

Abstract

We performed mutation analysis for genes implicated in long QT syndrome (KCNQ1, KCNH2, and SCN5A) in 17 sudden unexplained death autopsy cases. Single-strand conformation polymorphism and subsequent DNA sequencing analyses revealed that in one case, there was a variant, V207M of KCNQ1, a gene encoding a cardiac potassium channel. This case, a 40-year-old African male, was shown to have a heterozygous missense mutation (V207M), which has been previously reported to be ethnic-specific. The heterozygous V207M mutation was found in one case (0.23%) of 444 alleles from African individuals. We developed a knock-in mouse model carrier of the Kcnq1-V206M mutation, the mouse equivalent to the KCNQ1-V207M mutation identified in the victim. Significant prolongation of QT intervals was observed in the Kcnq1(V206M/V206M) mice. These findings suggest that the KCNQ1-V207M mutation might be pathogenic and might have been associated with the cause of death in the present case.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles*
  • Animals
  • Asian People / genetics*
  • Black People / genetics*
  • Child
  • DNA Mutational Analysis*
  • Death, Sudden, Cardiac / pathology*
  • Electrocardiography
  • Exons / genetics
  • Female
  • Gene Knock-In Techniques*
  • Genetic Carrier Screening
  • Genetic Variation / genetics*
  • Genetics, Population*
  • Homozygote
  • Humans
  • KCNQ1 Potassium Channel / genetics*
  • Long QT Syndrome / genetics*
  • Long QT Syndrome / pathology
  • Male
  • Mice
  • Mice, Transgenic / genetics
  • Mutation, Missense
  • Signal Processing, Computer-Assisted
  • Young Adult

Substances

  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human