title: A major deletion in the surfactant protein-B gene causing lethal respiratory distress.
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.
  
  
  OBJECTIVE
  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.
authors: Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, MO 63110, USA.
authors: Daniel J
authors: DJ
authors: Wegner
authors: Torbjörn
authors: T
authors: Hertzberg
authors: Hillary B
authors: HB
authors: Heins
authors: Göran
authors: G
authors: Elmberger
authors: Michael J
authors: MJ
authors: MacCoss
authors: Christopher S
authors: CS
authors: Carlson
authors: Lawrence M
authors: LM
authors: Nogee
authors: F Sessions
authors: FS
authors: Cole
authors: Aaron
authors: A
authors: Hamvas
mesh_terms: D020029:Base Pairing / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007231:Infant, Newborn; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics*; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics*
chemical_list: D037701:Pulmonary Surfactant-Associated Protein B