Not all congenital heart disease is inherited

YALE (US) — New mutations that are absent in parents but appear in their children account for at least 10 percent of severe congenital heart disease, a new study reveals.

The analysis of all the genes of more than 1800 individuals found hundreds of mutations that can cause congenital heart disease, the most common form of birth defect that afflicts nearly 1 percent of all newborns.

In particular, the study found frequent mutations in genes that modify histones, proteins that package DNA in the nucleus and orchestrate the timing and activation of genes crucial to development of the fetus.


“These findings provide new insight into the causes of this common congenital disease,” says senior author Richard Lifton, professor and chair of the department of genetics at Yale University.

“Most interestingly, the set of genes mutated in congenital heart disease unexpectedly overlapped with genes and pathways mutated in autism. These findings suggest there may be common pathways that underlie a wide range of common congenital diseases.”

The results of the study, part of the Pediatric Cardiac Genomics Consortium funded by the National Heart Lung and Blood Institute, were published in the journal Nature.

The mutations can occur at the same site, and both increase and decrease the modification histone proteins, says senior author Martina Brueckner, professor of pediatrics and genetics. The results suggest a very sensitive developmental system that might also be influenced by environmental factors in development.

“These findings point to fundamental mechanisms that play a role in a wide range of congenital diseases,” Lifton says.

Researchers from Columbia University Medical Center, the Perelman School of Medicine at University of Pennsylvania, and Harvard University shared senior authorship.

Source: Yale University