Abstract
Background: Loss of function mutations in the surfactant protein‐B gene (SFTPB) cause lethal neonatal respiratory distress due to reduced or absent expression of mature surfactant protein B (SP‐B, encoded in exons 6 and 7). No large deletions in SFTPB have been previously identified.
Aim: Genomic, proteomic and immunohistochemical characterization of a 3 kb deletion in SFTPB.
Methods: A full‐term newborn presented with refractory respiratory failure. We amplified and sequenced SFTPB from the infant and both parents, determined SP‐B protein expression in tracheal aspirate samples using Western‐blot analysis, and performed immunohistochemical staining and electron microscopy of lung biopsy tissue.
Results: The infant was homozygous for a 2958 bp deletion in SFTPB that included exons 7 and 8. Both asymptomatic parents were heterozygous for the deletion. A truncated mature SP‐B peptide was detected on Western blotting of tracheal aspirate. Amino acid sequence specific to that encoded in exon 5 was present, but that encoded by exon 7 was absent. ProSP‐B expression was robust within alveolar type II cells and lamellar body structure was disrupted.
Conclusions: This deletion in SFTPB resulted in SP‐B deficiency due to absence of elements in mature SP‐B that are critical for appropriate peptide folding, trafficking and processing.
