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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Atrioventricular Node / physiopathology
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Chromosome Mapping
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Chromosomes, Human, Pair 5
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Codon
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Female
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Genes, Dominant
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Genetic Linkage
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Heart Block / genetics*
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Heart Block / physiopathology
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Heart Septal Defects, Atrial / genetics*
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Heart Septal Defects, Atrial / physiopathology
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Homeobox Protein Nkx-2.5
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / metabolism
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Humans
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Male
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Mice
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Molecular Sequence Data
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Mutation
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Pedigree
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Protein Biosynthesis
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Xenopus Proteins*
Substances
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Codon
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Homeobox Protein Nkx-2.5
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Homeodomain Proteins
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NKX2-5 protein, human
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Nkx2-5 protein, mouse
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Transcription Factors
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Xenopus Proteins