Abstract
Mutations in genes encoding surfactant protein B (SP-B), ATP-binding cassette transporter A3 (ABCA3) and surfactant protein C (SP-C) can result in neonatal and pediatric lung disease. We retrospectively reviewed 391 molecular analyses of genes encoding SP-B (SFTPB), SP-C (SFTPC) and ABCA3 (ABCA3) performed in our laboratory from 2000 to 2015 in term and preterm newborn infants with severe respiratory distress syndrome (RDS), infants and children with interstitial lung disease (ILD), chorionic villi for prenatal diagnosis, parents and siblings of affected infants. Direct sequencing of SFTPB, SFTPC and ABCA3 was performed on genomic DNA extracted from peripheral blood. Histopathologic, immunohistochemical and ultrastructural analyses were performed when lung tissue was available. Genetic variants in SFTPB, SFTPC, ABCA3 were identified in 71 of 181 (39%) term and preterm newborn infants tested for severe and unexplained RDS and in 38 of 74 (51%) infants and children with ILD. A higher mortality rate was recorded among term newborn infants with homozygous or compound heterozygous mutations in SFTPB and ABCA3. Light microscopy and immunohistochemical analysis of the lung tissue were performed in 11 infants and electron microscopy in 8. Prenatal diagnosis was performed in 8 women with a previous child who died because of ABCA3 deficiency; 2 fetuses affected, 5 carriers and 1 normal were identified. Surfactant dysfunction was identified in a significant number of newborn infants with severe unexplained respiratory failure and children with ILD, indicating the importance of genetic studies in infants and children with this phenotype. While actual treatment is primarily supportive, early identification is important to establish appropriate management and evaluation of treatment options and to offer genetic counselling and prenatal diagnosis.
