Novel mutations of KCNQ1 in Long QT syndrome

Indian Heart J. Sep-Oct 2013;65(5):552-60. doi: 10.1016/j.ihj.2013.08.025. Epub 2013 Sep 4.

Abstract

Background: Autosomal recessive Long QT syndrome is characterized by prolonged QTc along with congenital bilateral deafness depends on mutations in K(+) channel genes. A family of a Long QT syndrome proband from India has been identified with novel indel variations.

Methods: The molecular study of the proband revealed 4 novel indel variations in KCNQ1. In-silico analysis revealed the intronic variations has led to a change in the secondary structure of mRNA and splice site variations. The exonic variations leads to frameshift mutations. DNA analysis of the available family members revealed a carrier status.

Results and conclusion: It is thus predicted that the variations may lead to a change in the position of the splicing enhancer/inhibitor in KCNQ1 leading to the formation of a truncated S2-S3 fragment of KCNQ1 transmembrane protein in cardiac cells as well as epithelial cells of inner ear leading to deafness and aberrant repolarization causing prolonged QTc.

Keywords: 3D KCNQ1 structure; Family study; JLN syndrome; Long QT syndrome; Novel mutations.

Publication types

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

MeSH terms

  • Child
  • DNA / analysis
  • DNA / genetics
  • Electrocardiography / methods
  • Frameshift Mutation / genetics*
  • Genetic Predisposition to Disease*
  • Genome
  • Heterozygote
  • Humans
  • India
  • Jervell-Lange Nielsen Syndrome / diagnosis
  • Jervell-Lange Nielsen Syndrome / genetics*
  • KCNQ1 Potassium Channel / genetics*
  • Long QT Syndrome / diagnosis
  • Long QT Syndrome / genetics*
  • Male
  • Molecular Biology
  • Pedigree
  • Polymerase Chain Reaction / methods
  • RNA / genetics
  • Rare Diseases

Substances

  • KCNQ1 Potassium Channel
  • RNA
  • DNA