Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science 1998 Jul 03;281(5373):108-11
Date
07/04/1998Pubmed ID
9651244DOI
10.1126/science.281.5373.108Scopus ID
2-s2.0-0032479573 (requires institutional sign-in at Scopus site) 1161 CitationsAbstract
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.
Author List
Schott JJ, Benson DW, Basson CT, Pease W, Silberbach GM, Moak JP, Maron BJ, Seidman CE, Seidman JGMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Atrioventricular Node
Chromosome Mapping
Chromosomes, Human, Pair 5
Codon
Female
Genes, Dominant
Genetic Linkage
Heart Block
Heart Septal Defects, Atrial
Homeobox Protein Nkx-2.5
Homeodomain Proteins
Humans
Male
Mice
Molecular Sequence Data
Mutation
Pedigree
Protein Biosynthesis
Transcription Factors
Xenopus Proteins
