Many Birth Defects in Heart Caused by Spontaneous Mutations

A study of children born with severe heart defects has found that at least 10 percent of cases stem from genetic mutations that occur spontaneously and affect heart development.

Such “de novo” mutations are not passed down from parent to child, but occur in the egg or sperm or just after fertilization.

Very little is known about the causes of congenital heart disease, so the discovery of these genes is a major step forward, say the study's authors, who conducted the research through the multi-center Pediatric Cardiac Genomics Consortium funded by the National Heart Lung and Blood Institute.

The study’s findings were published May 12 in Nature.

One of the study's senior authors, Wendy Chung, MD, PhD, professor of pediatrics and director of the Clinical Genetics Program at Columbia University Medical Center, says that the researchers took advantage of powerful new DNA technology to find the genes.

"We now have the ability to look at all the genes in the genome at once, not just one at a time, and that gives us the opportunity to find what causes congenital heart disease without having any prior knowledge or hypotheses," Chung says in a video produced by NHLBI.

Congenital heart disease is the most common birth defect in the United States, occurring in 1 out of every 100 births.

Many of these defects can be repaired surgically, but even among patients with the same defect and same surgery, outcomes vary. Some patients do well, others poorly.

The researchers say that understanding the genes behind congenital heart disease may give doctors a way to predict which patients will fare poorly and to improve treatments.

The types of genes uncovered by the present study should help researchers find even more genes important in congenital heart disease. "Some of the genes we found are active early in the process of heart development," Chung says, "and that will lead us to other genes that are active later in the process."

"Based on our study, we estimate that around 400 genes are involved in congenital heart disease," Chung adds, "so we still have quite a bit of work to do."

For more information about the study, see the NHLBI press release or watch the NHLBI-produced video with Chung and other authors of the new study: