First Common Gene Found for Congenital Heart Disease
Although congenital heart disease represents the most common major birth defect, scientists have not previously identified the common variation in the genes that give rise to it. Now genetics and cardiology researchers have discovered a genetic variant on chromosome 5 that strongly raises the risk of congenital heart disease.
“This gene, ISL1, plays a key role in regulating early cardiac development, so there is a compelling biological reason for investigating it as a genetic risk factor for CHD,” said study leader Peter J. Gruber, M.D., Ph.D., a pediatric cardiothoracic surgeon and developmental biologist at The Children’s Hospital of Philadelphia. Gruber collaborated with his brother, Stephen B. Gruber, M.D., Ph.D., a geneticist and epidemiologist at the University of Michigan Medical School.
The study appeared online in the journal Public Library of Science One. CHD affects at least one in 100 live births. It ranges widely in severity, from tiny holes between heart chambers that close naturally, to life-threatening abnormal structures such as hypoplastic left-heart syndrome that require a series of complicated surgeries. CHD can affect a variety of different structures in the heart, but the researchers decided to focus on the earliest period of the organ’s development. Instead of assuming separate genes would govern each specific defect; a hypothesis was formed that a common gene variant operates early in the biological pathway of heart formation, thus affecting multiple subtypes of congenital heart disease.
While the gene findings do not directly affect treatment for children with CHD, Peter Gruber said that better knowledge of the molecular basis of heart disease may provide eventual benefits for the children he sees as a surgeon. “As future studies better define exactly how a mutation leads to a specific type of heart defect, we may be better able to predict how a gene variant affects other organ systems,” he added. “We may be better able to understand how a child will respond to surgery, and when or even perhaps how to best perform perioperative, intra-operative or postoperative care. A greater understanding of molecular events in early development brings us that much closer to personalized medicine.”
