Hypermethylation of gene correlates with the presence of heart defects in Down's syndrome.

Congenital heart defects can decrease the quality of life and life expectancy in affected individuals, and constitute a major burden for the health care systems. Endocardial cushion defects are among the most prevalent heart malformations in the general population, and are extremely frequent (approximately a 100-fold higher prevalence) in children with Down syndrome. Several genes have been proposed to be involved in the pathogenesis of these malformations, but no common pathogenic DNA variants have been identified so far. Here, we focussed on constitutive, epigenetic alterations of function of selected genes, potentially important for endocardial cushion development. We used two types of microarrays, dedicated for assessment of gene promoter methylation and whole genome expression. First, we compared the gene promoter methylation profiles between two groups of Down syndrome patients, with and without heart defects of endocardial cushion-type. Then, to determine the functional role of the detected methylation alterations, we assessed the expression of the genes of interest. We detected significant hypermethylation of the gene promoter region in children with heart defects. is a key factor in maturation of endocardial cushions. Supplementary gene expression assessment revealed significantly decreased activity of the , and genes in children with heart defects. The above three genes are closely related to the gene and are crucial elements of the NRG/ErbB pathway. The results of this pilot study show that hypermethylation of the gene promoter can reflect the functional genome alteration contributing to development of congenital heart defects of endocardial cushion-type.