Loss-of-function mutations in growth differentiation factor-1 (GDF1) are associated with congenital heart defects in humans

J. D. Karkera, J. S. Lee, E. Roessler, S. Banerjee-Basu, M. V. Ouspenskaia, J. Mez, E. Goldmuntz, P. Bowers, Jeffrey Towbin, J. W. Belmont, A. D. Baxevanis, A. F. Schier, M. Muenke

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Congenital heart defects (CHDs) are among the most common birth defects in humans (incidence 8-10 per 1,000 live births). Although their etiology is often poorly understood, most are considered to arise from multifactorial influences, including environmental and genetic components, as well as from less common syndromic forms. We hypothesized that disturbances in left-right patterning could contribute to the pathogenesis of selected cardiac defects by interfering with the extrinsic cues leading to the proper looping and vessel remodeling of the normally asymmetrically developed heart and vessels. Here, we show that heterozygous loss-of-function mutations in the human GDF1 gene contribute to cardiac defects ranging from tetralogy of Fallot to transposition of the great arteries and that decreased TGF-β signaling provides a framework for understanding their pathogenesis. These findings implicate perturbations of the TGF-β signaling pathway in the causation of a major subclass of human CHDs.

Original languageEnglish (US)
Pages (from-to)987-994
Number of pages8
JournalAmerican Journal of Human Genetics
Volume81
Issue number5
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

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Growth Differentiation Factor 1
Congenital Heart Defects
Mutation
Transposition of Great Vessels
Tetralogy of Fallot
Live Birth
Causality
Cues
Incidence
Genes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Karkera, J. D., Lee, J. S., Roessler, E., Banerjee-Basu, S., Ouspenskaia, M. V., Mez, J., ... Muenke, M. (2007). Loss-of-function mutations in growth differentiation factor-1 (GDF1) are associated with congenital heart defects in humans. American Journal of Human Genetics, 81(5), 987-994. https://doi.org/10.1086/522890

Loss-of-function mutations in growth differentiation factor-1 (GDF1) are associated with congenital heart defects in humans. / Karkera, J. D.; Lee, J. S.; Roessler, E.; Banerjee-Basu, S.; Ouspenskaia, M. V.; Mez, J.; Goldmuntz, E.; Bowers, P.; Towbin, Jeffrey; Belmont, J. W.; Baxevanis, A. D.; Schier, A. F.; Muenke, M.

In: American Journal of Human Genetics, Vol. 81, No. 5, 01.01.2007, p. 987-994.

Research output: Contribution to journalArticle

Karkera, JD, Lee, JS, Roessler, E, Banerjee-Basu, S, Ouspenskaia, MV, Mez, J, Goldmuntz, E, Bowers, P, Towbin, J, Belmont, JW, Baxevanis, AD, Schier, AF & Muenke, M 2007, 'Loss-of-function mutations in growth differentiation factor-1 (GDF1) are associated with congenital heart defects in humans', American Journal of Human Genetics, vol. 81, no. 5, pp. 987-994. https://doi.org/10.1086/522890
Karkera, J. D. ; Lee, J. S. ; Roessler, E. ; Banerjee-Basu, S. ; Ouspenskaia, M. V. ; Mez, J. ; Goldmuntz, E. ; Bowers, P. ; Towbin, Jeffrey ; Belmont, J. W. ; Baxevanis, A. D. ; Schier, A. F. ; Muenke, M. / Loss-of-function mutations in growth differentiation factor-1 (GDF1) are associated with congenital heart defects in humans. In: American Journal of Human Genetics. 2007 ; Vol. 81, No. 5. pp. 987-994.
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