Compound SFTPB 1549C→GAA (121ins2) and 457delC heterozygosity in severe congenital lung disease and surfactant protein B (SP-B) deficiency

✍ Scribed by Mohammed Tredano; Ruurd M. van Elburg; Ageeth G. Kaspers; Luc J. Zimmermann; Claude Houdayer; Pierre Aymard; William M. Hull; Jeffrey A. Whitsett; Jacques Elion; Matthias Griese; Michel Bahuau

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 337 KB
• Volume: 14
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/(sici)1098-1004(199912)14:6<502::aid-humu9>3.0.co;2-c

✦ Synopsis

Communicated by Michel Goossens

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. Hum Mutat 14:502-509, 1999.