A major deletion in the surfactant protein-B gene causing lethal respiratory distress.
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.
Wegner
Daniel J
DJ
Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, MO 63110, USA.
Hertzberg
Torbjörn
T
Heins
Hillary B
HB
Elmberger
Göran
G
MacCoss
Michael J
MJ
Carlson
Christopher S
CS
Nogee
Lawrence M
LM
Cole
F Sessions
FS
Hamvas
Aaron
A
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*
D037701:Pulmonary Surfactant-Associated Protein B