Two young NRI medical researchers, Dr. Deepak Srivastava and Dr. Vidu Garg, have identified a gene that plays a role in the development of congenital heart defects. The gene, known as GATA4, is the second gene that has been identified as a possible cause of congenital heart defects, one of the most common birth defects in the United States of America.

"This gene is in a class of master regulators. It turns other genes on or off," says study author Dr. Srivastava, an Associate Professor of Paediatrics and Molecular Biology at the University of Texas Southwestern in Dallas. A mutation in this gene affects its function, says Srivastava, which prevents GATA4 from turning on other genes that are responsible for tasks such as forming a baby’s heart walls early in pregnancy. The result is a congenital heart defect, often literally a hole in the heart or a problem with the heart’s valves. Slightly less than one per cent of American babies, or about 35,000 annually, have a congenital heart defect, according to the American Heart Association. Congenital heart defects remain the leading birth defect-related cause of death in infants, according to the March of Dimes.

Results of the study appear in the July 6 issue of Nature.

Dr. Garg, Assistant Professor of Paediatrics at Southwestern, said: "In terms of the genetic origins, there are not many discoveries that have been made. "This is one of the genes responsible, and we are working to identify others. We cannot change the fact that parents are going to pass along the mutation, but we might be able to develop a way to keep the disease from occurring."

To locate a mutation in GATA4, the researchers examined two large families with a strong history of congenital heart defects. The first family was from Dallas and included five generations. Sixteen members of that family were born with congenital heart defects. The researchers performed a test known as a linkage scan that looks for differences in the genes of those who are affected by a disorder and those who are not. All the family members with heart defects had a mutation in GATA4, while the healthy family members did not.

To confirm their findings, the researchers collaborated with Japanese researchers who had discovered a family spanning four generations with eight members with congenital heart defects. The results were the same as they were in the Dallas family.

Using data from the Dallas group, the researchers found that the GATA4 mutation interfered with the gene’s ability to interact with another gene responsible for early heart formation, TBX5, pointing to a possible cause for the heart defect.

Knowing the cause may eventually lead to therapies for prevention in much the same way that folic acid has helped reduce neural tube defects, another class of birth defects, says Srivastava.

"The most immediate application is for families that have the mutation," he says. "We can provide very accurate genetic counselling and can test for the mutation. If the parents have the mutation, the risk of passing it on is 50 per cent. If they don’t have the mutation, the risk is zero per cent."