Of mice and men: molecular genetics of congenital heart disease

Abstract

Congenital heart disease (CHD) affects nearly 1 % of the population. It is a complex disease, which may be caused by multiple genetic and environmental factors. Studies in human genetics have led to the identification of more than 50 human genes, involved in isolated CHD or genetic syndromes, where CHD is part of the phenotype. Furthermore, mapping of genomic copy number variants and exome sequencing of CHD patients have led to the identification of a large number of candidate disease genes. Experiments in animal models, particularly in mice, have been used to verify human disease genes and to gain further insight into the molecular pathology behind CHD. The picture emerging from these studies suggest that genetic lesions associated with CHD affect a broad range of cellular signaling components, from ligands and receptors, across down-stream effector molecules to transcription factors and co-factors, including chromatin modifiers.

Fig. 1

Schematic representation of the different cell signaling components affected by mutations in human CHD disease genes. These include ligands (L), receptors (R), down-stream effectors (E), transcription regulators, which include transcription factors (TF), transcription co-factors (co-TF) and histone modifying proteins (HM), and target genes. Known human CHD disease genes within the six groups are shown in the panel at the right. Colored figure are shown in the on-line version of the article