A study published in the online journal Nature reports that 10 percent of severe congenital heart defects are caused by new gene mutations that were not passed down by the children’s parents.
According to the National Heart, Lung and Blood Institute (NHLBI), congenital heart defects are the most common type of birth defect, affecting eight out of every 1,000 newborns. Each year, more than 35,000 babies in the U.S. are born with congenital heart defects.
“One of the most important questions when a family has a child with congenital heart disease is why?” Dr. Edwin Kirk, a clinical geneticist at Sydney Children’s Hospital in Australia, told Bloomberg Businessweek.
“Any research that helps us understand the answer hopefully will one day be something we can apply to answer the question for individual families,” added Kirk, who was not involved in the research.
Surgical advances over the last decade have allowed children born with heart defects to live well into adulthood. However, knowledge of the causes of the defects has lagged.
“You don’t know what possible therapies are available until you get a better understanding of what’s going on at a fundamental level,“ Jonathan Kaltman, chief of heart development and structural diseases science at the NHLBI, and co-author of the study, told the Wall Street Journal.
To gain that “understanding,” researchers from nine U.S. medical centers and one in Great Britain mapped the DNA of 362 children and young adults born with serious heart defects, but whose parents did not have congenital heart disease. The genes of a control group of 264 healthy babies were also analyzed.
Researchers found that while both groups had de novo mutations – new mutations that arise spontaneously and are not inherited – the children with congenital heart defects were more likely to carry damaging mutations at two sites within a particular cellular pathway known to regulate genes that are key to heart development.
“These findings provide new insight into the causes of this common congenital disease,” said senior study author Richard Lufton, chair of the department of genetics at the Yale School of Medicine, in a news release.
In a surprise finding, researchers also noted an overlap with mutations associated with autism.
“Most interestingly,” said Lufton in the Yale news release, “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.”
Lufton and his colleagues plan more studies to identify the genetic architecture underlying congenital heart disease in the hopes of discovering additional therapies that will help doctors better care for children with heart defects.
“After we repair the hearts of these children, some children do great and some do poorly,” Dr. Christine E. Seidman, study co-author, and a Howard Hughes Medical Institute Investigator at Brigham and Women’s Hospital in Boston, told the Wall Street Journal.
“Researchers have long suspected that this might be due to differences in the underlying causes of the disease. Understanding those variations might help doctors improve those outcomes for their patients,” added Seidman.
