Genes in congenital heart disease: atrioventricular valve formation

Abstract

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.

How to Make a Heart Valve: From Embryonic Development to Bioengineering of Living Valve Substitutes

“…Multiple types of progenitor cells, originating from both inand outside the heart orchestrate valve morphogenesis through highly conserved signaling networks. Once again, mistiming or malfunction of the unfolding events cause valvuloseptal de-fects in patients with congenital heart disease and in experimental animal models (Srivastava 2006;Joziasse et al 2008;Lin et al 2012). …”

Functional Analysis of Two Novel Mutations in TWIST1 Protein Motifs Found in Ventricular Septal Defect Patients

“…Epithelial-mesenchymal transitions are vital for the development of cardiac cushions, which is required for septation of the heart [27]. TWIST1 regulates epithelialmesenchymal transitions through a mechanism involving repression of E-cadherin transcription and directly binds to E-boxes in the promoter region of the E-cadherin gene [28,39].…”

Characterization of molecular markers to assess cardiac cushions formation in Xenopus

“…Abnormal septation of the heart and valve anomalies are the most frequent forms of congenital heart defects (reviewed in Joziasse et al, 2008).…”