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.
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.
Authors: Lindsay B Henderson; Kristin Melton; Susan Wert; Jonathan Couriel; Andrew Bush; Michael Ashworth; Lawrence M Nogee Journal: Ann Am Thorac Soc Date: 2013-12
Authors: Geoffrey Kurland; Robin R Deterding; James S Hagood; Lisa R Young; Alan S Brody; Robert G Castile; Sharon Dell; Leland L Fan; Aaron Hamvas; Bettina C Hilman; Claire Langston; Lawrence M Nogee; Gregory J Redding Journal: Am J Respir Crit Care Med Date: 2013-08-01 Impact factor: 21.405
Authors: Aaron Hamvas; Lawrence M Nogee; Daniel J Wegner; Kelcey Depass; John Christodoulou; Bruce Bennetts; Leon R McQuade; Peter H Gray; Robin R Deterding; Travis R Carroll; Anja Kammesheidt; Laura M Kasch; Shashikant Kulkarni; F Sessions Cole Journal: J Pediatr Date: 2009-08-03 Impact factor: 4.406