Congenital Heart Disease Caused by Mutations in the Transcription Factor NKX2-5

JJ Schott, DW Benson, CT Basson, W Pease… - Science, 1998 - science.org
JJ Schott, DW Benson, CT Basson, W Pease, GM Silberbach, JP Moak, BJ Maron…
Science, 1998science.org
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 …
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.
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