Researchers identify genetic mechanisms behind congenital heart disease

Researchers have identified new genetic mechanisms contributing to congenital heart disease, a condition affecting approximately 1 in 100 infants. Studies published in Science and Science China Life Sciences highlight how disruptions in DNA structure and regulatory switches impact heart development.

At the Gladstone Institutes, scientists discovered that the TBX5 gene acts as an architect for the three-dimensional structure of DNA in heart cells. Losing just one copy of TBX5 can cause the genome's physical folding to unravel, disrupting the expression of other genes necessary for building a healthy heart. This finding helps explain why individuals with the same mutation may experience different types of heart defects.

In a separate study, researchers from Nanjing Medical University investigated tetralogy of Fallot, a common cyanotic heart defect. By sequencing the entire genomes of 428 patients, the team identified functional variants in non-coding DNA that act as switches. These switches control the regulation of genes like TBX1, which is critical for the development of the heart's outflow tract. The research suggests that defects can arise not just from broken genes, but from the loss of regulatory elements that control gene activity.