Each year, approximately 40,000 babies are born in the United States with congenital heart disease. Many of these birth defects are fatal without surgical intervention. The causes of most cases are unknown, but new findings by two HHMI investigators indicate that spontaneous mutations are the culprit in some cases.
Although genetic factors contribute to congenital heart disease, many children born with heart defects have healthy parents and siblings, hinting that the responsible mutations might not be present in the parents. Richard Lifton of the Yale School of Medicine and Christine Seidman of Brigham and Women’s Hospital led a team of scientists that analyzed the protein-coding regions of the genomes—exomes—of more than 1,800 individuals with and without the disease. The team discovered that about 10 percent of children’s heart defects are caused by spontaneous, or de novo, genetic mutations. Strikingly, as they reported June 13, 2013, in Nature, many of these mutations affect a pathway that regulates modification of proteins called histones, a pathway also implicated in children with neurodevelopmental problems.
The findings may help physicians provide better care for patients with congenital heart disease. “After we repair the hearts of these children, some children do great and some do poorly,” Seidman says. This could be due to differences in the underlying causes of the disease. Understanding those variations might help doctors improve outcomes for their patients.