A team of US-based researchers said they have identified a mutation in the ABCA3 gene that may increase the risk of developing a severe lung disease that appears in infants.
The results appear to confirm earlier reports that a mutation in the gene “leads to serious lack” of a surfactant, a chemical that helps prevent lungs from collapsing. Previous studies suggested that mutations in the ABCA3 gene have toxic effects on lung metabolism in infants.
In their study, the researchers identified 21 infants with severe lung disease and surfactant deficiency “of unknown causes,” but whose family medical histories “suggested a genetic basis” for the illnesses. Results showed that mutations in ABCA3 existed in 16 infants, 14 of whom died due to the illness. Three of the five infants without the mutation “recovered completely,” and one died of unknown causes, the researchers noted.
Lawrence Nogee, a study author and neonatologist at the Cincinnati Children’s Hospital Medical Center, suggested that since the gene belongs to a family of transporter proteins, a mutated version “may actually carry away the phospholipids … critical for surfactant function,” according to a statement released by the hospital last week.
“This kind of defective transport could lead to the production of abnormal surfactant, or, alternatively, a mutated ABCA3 gene could transport in lipids toxic to surfactant production,” Nogee said in the statement.
However, he stressed that because one infant with the mutation survived the disease, “some” ABCA3 mutations may not be fatal. “Our findings provide yet another clue as to what may trigger surfactant deficiency and neonatal lung disease, but the absence of an ABCA3 mutation in at least one infant in our study who developed fatal lung disease indicates that there are still other genes yet to be identified in this disease,” Nogee said in the statement.
One way to do this, he said, is to study the prevalence of ABCA3 mutations in the general population to determine which ones lead to disease.
The research appears in this week’s New England Journal of Medicine.
“The study provides new insight into how the lung functions,” Michael Dean, a senior author on the study and a researcher at the National Cancer Institute’s Laboratory of Genomic Diversity, said in a statement. “The lung surfactants that ABCA3 helps produce are essential for breathing and this work may provide insight into other pulmonary diseases.”