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

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Science  03 Jul 1998:
Vol. 281, Issue 5373, pp. 108-111
DOI: 10.1126/science.281.5373.108

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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.

  • * These authors contributed equally to this work.

  • Present address: Cardiovascular Genetics, Medical University of South Carolina, Charleston, SC 29451, USA.

  • Present address: Cardiovascular Division, Cornell University Medical College, New York, NY 10021, USA.

  • § To whom correspondence should be addressed. E-mail: seidman{at}

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