Congenital heart disease caused by mutations in the transcription factor NKX2-5

Science. 1998 Jul 3;281(5373):108-11. doi: 10.1126/science.281.5373.108.

Abstract

Mutations in the gene encoding the homeobox transcription factor NKX2-5 were found to cause nonsyndromic, human congenital heart disease. A dominant disease locus associated with cardiac malformations and atrioventricular conduction abnormalities was mapped to chromosome 5q35, where NKX2-5, a Drosophila tinman homolog, is located. Three different NKX2-5 mutations were identified. Two are predicted to impair binding of NKX2-5 to target DNA, resulting in haploinsufficiency, and a third potentially augments target-DNA binding. These data indicate that NKX2-5 is important for regulation of septation during cardiac morphogenesis and for maturation and maintenance of atrioventricular node function throughout life.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Atrioventricular Node / physiopathology
  • Chromosome Mapping
  • Chromosomes, Human, Pair 5
  • Codon
  • Female
  • Genes, Dominant
  • Genetic Linkage
  • Heart Block / genetics*
  • Heart Block / physiopathology
  • Heart Septal Defects, Atrial / genetics*
  • Heart Septal Defects, Atrial / physiopathology
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Pedigree
  • Protein Biosynthesis
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Xenopus Proteins*

Substances

  • Codon
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins
  • NKX2-5 protein, human
  • Nkx2-5 protein, mouse
  • Transcription Factors
  • Xenopus Proteins