Basic Research in Cardiology

, Volume 103, Issue 3, pp 216-227

First online:

Genes in congenital heart disease: atrioventricular valve formation

  • Irene C. JoziasseAffiliated withDept. of Cardiology E03.511, University Medical Center Utrecht
  • , Jasper J. van de SmagtAffiliated withDept. of Medical Genetics, University Medical Center Utrecht
  • , Kelly SmithAffiliated withHubrecht Laboratory
  • , Jeroen BakkersAffiliated withHubrecht Laboratory
  • , Gert-Jan SieswerdaAffiliated withDept. of Cardiology E03.511, University Medical Center Utrecht
  • , Barbara J. M. MulderAffiliated withDept. of Cardiology, Amsterdam Medical Center
  • , Peter A. DoevendansAffiliated withDept. of Cardiology E03.511, University Medical Center Utrecht Email author 

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Through the use of animal studies, many candidate genes (mainly encoding transcriptional factors and receptors) have been implicated in the development of congenital heart disease. Thus far, only a minority of these genes have been shown to carry mutations associated with congenital disease in humans, e.g., GATA 4, TBX-5, NOTCH1 and NKX2-5. Mutations in these genes can cause a variety of cardiac defects even within the same family. Conversely, similar phenotypes are observed for different gene mutations suggesting a common pathway. Multiple genes and genetic pathways have been related to atrioventricular valve formation, although most of these genes have not yet been demonstrated as causative in human atrioventricular valve defects. Key pathways include the epidermal growth factor receptor pathway and related interacting pathways, most importantly the pathway of UDP-glucose dehydrogenase, resulting ultimately in activation of Ras. Other examples of interacting pathways include that of Nodal/Cited2/Pitx2, Wnt, Notch and ECE. Further studies are needed to investigate the pathways which are crucial for atrioventricular valve formation in humans. Understanding the underlying molecular process of abnormal atrioventricular valve formation in patients with congenital heart disease may provide important insight, in the etiology and possibly into preventive or treatment regimes.

Key words

heart defects congenital valves genes genetic pathways