Their findings, reported in this week's New England Journal of Medicine, confirm that mutations in the ABCA3 gene lead to a serious lack of surfactant, a mixture of fats and proteins that enables lung expansion and contraction and maintains the low surface tension needed to prevent lung collapse.
Study co-author Lawrence Nogee, M.D., a neonatologist at the Children's Center, speculates that since the ABCA3 gene is related to a family of transporter proteins, the defective ABCA3 protein may shuttle the phospholipids (compounds of fatty acids, phosphoric acid and a nitrogenous base) critical for surfactant function into the compartment in the cell where surfactant is stored. "This kind of defective transport could lead to the production of abnormal surfactant, or, alternatively, a mutated ABCA3 gene could fail to transport out lipids toxic to surfactant function," he says.
Researchers zeroed in on ABCA3 as a candidate gene for unexplained surfactant deficiency in full-term infants because of other ABC genes' links with human diseases, the cellular location of ABCA3, and ABCA3's already suspected involvement in transporting lipids, says Nogee.
In the study, researchers first identified 21 infants with severe lung disease and surfactant deficiency of unknown causes, but whose family medical histories suggested a genetic basis for their problems. Mutations in ABCA3 were found in 16 infants, 15 of whom died of their illness. Of the five patients without ABCA3 mutations, three infants recovered completely. Two later died from their lung disease.