Researchers Identify Gene Related To Infant Lung Disease

"These fundamental investigations will allow us to develop more sophisticated therapies for respiratory problems," says Aaron Hamvas, M.D., associate professor of pediatrics at Washington University School of Medicine in St. Louis. "We now are one step closer to identifying another type of genetic lung disease, but we still have a long way to go."

Hamvas, who also serves on the staff of St. Louis Children’s Hospital, is a collaborator in this study along with researchers at the University of Cincinnati and Johns Hopkins University. The first author is Lawrence M. Nogee, M.D., of Johns Hopkins University School of Medicine.

These three institutions have investigated hundreds of cases of lung disease from around the world in an effort to better understand the underlying causes of the disease. Such was the case with the mother-daughter pair described in this report. Both mother and daughter had no breathing difficulties at birth but subsequently developed interstitial lung disease. The exact number of chronic lung disorders in this disease category still is unknown.

Diagnosed as a toddler, the mother was treated throughout her childhood and adolescence. She died of respiratory failure shortly after the birth of her child.

Her infant girl developed lung disease at 6 weeks old. A family history revealed that the baby’s maternal grandfather also died of life-long lung disease.

The tiny air sacs responsible for gas exchange in the lungs are called alveoli. These are lined with a thin layer of fluid, called surfactant, to prevent the walls of the alveoli from sticking together and collapsing during exhalation. Without enough surfactant, the lungs lose their elasticity and breathing becomes difficult.

Researchers found that tissue samples from both mother and baby lacked one component of surfactant called surfactant protein C, or SP-C. DNA analysis revealed that both had a mutation in the gene for this protein. The gene was not mutated in DNA samples from 50 healthy patients.

The findings suggest that SP-C is important for normal lung function after birth and that mutations in this gene may be associated with interstitial lung disease.

In 1993, researchers at Washington University School of Medicine discovered a lethal genetic lung disease in newborns characterized by a lack of another component of surfactant, SP-B. Newborns with this disease now survive with the help of a lung transplant.

"The identification of the SP-B deficiency has opened a new area of investigation for newborn lung disease and suggests that there are genetic causes of respiratory distress in newborns," Hamvas says. "This has led physicians