CHOP Scientist Collaborates in Heart Disease Gene Study

Published on in CHOP News

May 13, 2013 — A physician-researcher from The Children’s Hospital of Philadelphia, Elizabeth Goldmuntz, MD, is one of the senior leaders of a research consortium reporting important gene changes that may help explain why children are born with heart defects.

CHOP is one of five centers in the Pediatric Cardiac Genetics Consortium, supported by the National Heart, Lung and Blood Institute, part of the National Institutes of Health. The Consortium published its first major study findings in an advance online publication on May 12 in Nature.

The current study identified de novo mutations predicted to be protein altering in genes expressed in the developing heart. The mutations were particularly abundant in histone-modifying genes—genes that play key roles in early human development by affecting whether other genes become active. De novo mutations are changes in the gene sequence that are not present in the parents but found only in the affected child as a new alteration. Because these mutations were predicted to change protein function, they are likely to be deleterious.

The researchers compared 362 families in which a child had a severe heart defect to 264 control families, analyzing their exomes — the protein-coding sections of DNA — to determine which mutations were more common in severe cases.

“Collectively, these results suggest that protein-altering, de novo point mutations occur in hundreds of genes, and may account for about 10 percent of severe congenital heart disease,” said Dr. Goldmuntz, the consortium’s principal investigator at CHOP and a pediatric cardiologist at CHOP’s Cardiac Center. “Congenital heart disease itself is the most frequent serious birth defect, so as we go on to discover more of these gene alterations during early heart development, we will be better able to provide genetic counseling and refine patient care for many families and children.”

In addition to CHOP, the other four centers in the Pediatric Cardiac Genetics Consortium are Yale University, Columbia University, Mt. Sinai School of Medicine, and Harvard University.


John Ascenzi, Children’s Hospital of Philadelphia, Phone: 267-426-6055,