title: Prolonged survival in hereditary surfactant protein B (SP-B) deficiency associated with a novel splicing mutation.
abstract: Hereditary surfactant protein B (SP-B) deficiency has been lethal in the first year of life without lung transplantation. We tested the hypothesis that SP-B gene mutations may result in milder phenotypes by investigating the mechanisms for lung disease in two children with less severe symptoms than have been previously observed in SP-B deficiency. Immunostaining patterns for pulmonary surfactant proteins were consistent with SP-B deficiency in both children. DNA sequence analysis indicated that both children were homozygous for a mutation in exon 5 that created an alternative splice site. Reverse transcriptase PCR and sequence analysis confirmed use of this splice site, which resulted in a frameshift and a premature termination codon in exon 7. The predominant reverse transcriptase PCR product, however, lacked exon 7, which restored the reading frame but would not allow translation of the exons that encode mature SP-B. Western blot analysis detected reduced amounts of mature SP-B as well as an aberrant SP-B proprotein that corresponded to the size expected from translation of the abnormal transcript. We conclude that a novel splicing mutation was the cause of lung disease in these children and that hereditary SP-B deficiency can be the cause of lung disease in older children.
authors.affiliation: Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland 21287, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Dunbar
authors.forename: S E
authors.initials: SE
authors.lastname: Wert
authors.forename: M
authors.initials: M
authors.lastname: Ikegami
authors.forename: J A
authors.initials: JA
authors.lastname: Whitsett
authors.forename: A
authors.initials: A
authors.lastname: Hamvas
authors.forename: F V
authors.initials: FV
authors.lastname: White
authors.forename: B
authors.initials: B
authors.lastname: Piedboeuf
authors.forename: C
authors.initials: C
authors.lastname: Jobin
authors.forename: S
authors.initials: S
authors.lastname: Guttentag
authors.forename: L M
authors.initials: LM
authors.lastname: Nogee
mesh_terms: D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D008171:Lung Diseases / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D011663:Pulmonary Surfactants / Q000172:deficiency* / Q000235:genetics*; D012326:RNA Splicing
chemical_list: D011663:Pulmonary Surfactants