GNN - Genome News Network  
  Home | About | Topics
Congenital heart disease may be inherited after all
Edward R. Winstead

Scientists have mapped a gene in a common heart disease that had previously been thought to occur randomly during fetal development and whose genetic origins were unclear. Now, it appears that inheriting two copies of a single gene may predispose individuals to the disorder, which typically affects newborns and is known as PDA (patent ductus arteriosus).

Cross-section of term PDA. View larger

The second most common congenital heart disease, PDA occurs when a major artery in the fetus fails to close at birth. Newborns may experience shortness of breath, pulmonary hypertension and heart failure. The condition can also lead to health problems during adolescence and adulthood; some individuals develop heart murmurs.

"The disease can manifest itself at different stages of a person's life," says Arya Mani, of the Yale University School of Medicine in New Haven, Connecticut, and a member of the research team. "When a child is born, he or she may have shortness of breath and be distressed." The treatment involves closing the vessel surgically or with catheter devices.

The origins of PDA have been unclear, but studies in mice have suggested that individual genes may play significant roles. Recessive diseases exist everywhere, but finding recessive genes is easiest in closely related populations because a particular stretch of DNA will show up more frequently.

In this study, the researchers recruited families with PDA in Iran, where marriage between related individuals occurs 25 percent of the time.

To map the gene, a team led by Richard P. Lifton, also of Yale, obtained DNA from 21 families in which the parents were first or second cousins. Though the gene has not yet been isolated, it maps to a region of chromosome 12. The findings were published online in Proceedings of the National Academy of Sciences.

The strategy of studying families in which close relatives marry is particularly useful in dissecting the origins of recessive disorders that appear to occur randomly in the population. Other researchers have hunted for genes involved in inherited diseases in Saudi Arabia, India, Italy, and parts of Latin America.

"Many groups are finding genes for diseases that we once thought were sporadic, particularly among cardiovascular diseases," says Mani. "Our evidence is that these are caused by genes and have a genetic basis."

Whether the recessive PDA gene, when mutated, is sufficient to cause the disorder is not known. Other genes and environmental factors may modify or influence the development of the disease.

In trying to understand the genetics of complex diseases, it will be important to have contributions from clinicians who study inbred populations, says Mani.

"There are very good clinicians in many countries such as Iran who are willing and eager to collaborate," says Mani. "They are thirsty for knowledge, and when you give them a task they really go after it."

. . .

Mani, A. et al. Finding genetic contributions to sporadic disease: A recessive locus at 12q24 commonly contributes to patent ductus arteriosus. Proc Natl Acad Sci USA. Published online October 30, 2002.

Back to GNN Home Page