title: Compound SFTPB 1549C-->GAA (121ins2) and 457delC heterozygosity in severe congenital lung disease and surfactant protein B (SP-B) deficiency.
abstract: Several human respiratory disorders have been linked to an abnormality of pulmonary surfactant synthesis or turnover. Among those conditions, hereditary deficiency in the hydrophobic surfactant protein B (SP-B) has been recognized as a rare cause of respiratory failure in term newborn infants. Homozygosity for a common mutation (1549C-->GAA, or 121ins2) of the SP-B-encoding gene (SFTPB) results in rapidly fatal respiratory failure, with complete absence of the mRNA and protein observed in lung fluid or biopsy specimens. Hereditary SP-B deficiency is also associated with aberrant processing of proSP-C and deficiency of the active SP-C peptide. In the present study, we characterized the SFTPB gene in an infant with severe unexplained respiratory distress and identified a paternally derived 1549C-->GAA lesion, as well as a hitherto unreported mutation (457delC) inherited from the mother. Analysis of bronchoalveolar lavage fluid demonstrated the complete absence of SP-B. However, unlike previous infants with hereditary SP-B deficiency, proSP-C was processed to the active SP-C peptide, suggesting that the defect in SP-B, rather than SP-C, caused the respiratory distress in this infant. The present findings demonstrate the importance of SFTPB in pulmonary function and support the need for further genotype-phenotype correlations in patients with SP-B deficiency.
authors.affiliation: Service de Biochimie et Biologie Moléculaire, Hôpital d'Enfants Armand-Trousseau, Paris, France. biochimie.trousseau@trs.ap-hop-paris.fr
authors.forename: M
authors.initials: M
authors.lastname: Tredano
authors.forename: R M
authors.initials: RM
authors.lastname: van Elburg
authors.forename: A G
authors.initials: AG
authors.lastname: Kaspers
authors.forename: L J
authors.initials: LJ
authors.lastname: Zimmermann
authors.forename: C
authors.initials: C
authors.lastname: Houdayer
authors.forename: P
authors.initials: P
authors.lastname: Aymard
authors.forename: W M
authors.initials: WM
authors.lastname: Hull
authors.forename: J A
authors.initials: JA
authors.lastname: Whitsett
authors.forename: J
authors.initials: J
authors.lastname: Elion
authors.forename: M
authors.initials: M
authors.lastname: Griese
authors.forename: M
authors.initials: M
authors.lastname: Bahuau
mesh_terms: D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011510:Proteolipids / Q000235:genetics* / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000235:genetics* / Q000378:metabolism; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: D017931:DNA Primers; D011510:Proteolipids; D011663:Pulmonary Surfactants