Research Article

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

  1. Mohammed Tredano1,*,
  2. Ruurd M. van Elburg2,
  3. Ageeth G. Kaspers2,
  4. Luc J. Zimmermann3,
  5. Claude Houdayer1,
  6. Pierre Aymard1,
  7. William M. Hull4,
  8. Jeffrey A. Whitsett4,
  9. Jacques Elion5,
  10. Matthias Griese6,
  11. Michel Bahuau1,*

Article first published online: 22 NOV 1999

DOI: 10.1002/(SICI)1098-1004(199912)14:6<502::AID-HUMU9>3.0.CO;2-C

Issue

Human Mutation

Human Mutation

Volume 14, Issue 6, pages 502–509, December 1999

Additional Information

How to Cite

Tredano, M., van Elburg, R. M., Kaspers, A. G., Zimmermann, L. J., Houdayer, C., Aymard, P., Hull, W. M., Whitsett, J. A., Elion, J., Griese, M. and Bahuau, M. (1999), Compound SFTPB 1549C→GAA (121ins2) and 457delC heterozygosity in severe congenital lung disease and surfactant protein B (SP-B) deficiency. Human Mutation, 14: 502–509. doi: 10.1002/(SICI)1098-1004(199912)14:6<502::AID-HUMU9>3.0.CO;2-C

Author Information

  1. 1

    Service de Biochimie et Biologie Moléculaire, Hôpital d'Enfants Armand-Trousseau, Paris, France

  2. 2

    Vrije Universiteit, Academisch Ziekenhuis, Amsterdam, The Netherlands

  3. 3

    Neonatology, Sophia Children's Hospital, University Hospital Rotterdam, Erasmus University Rotterdam, Rotterdam, The Netherlands

  4. 4

    Division of Pulmonary Biology, Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

  5. 5

    Service de Biochimie Génétique, Hôpital Robert-Debré, Paris, France

  6. 6

    Kinderklinik und Kinderpoliklinik, Dr. von Haunerschen Kinderspital, Ludwig-Maximilians Universität, München, Federal Republic of Germany

*Service de Biochimie et Biologie Moléculaire, Hôpital d'Enfants Armand-Trousseau, 26 Avenue du Docteur Arnold-Netter, 75571 Paris Cedex 12, France

Publication History

  1. Issue published online: 22 NOV 1999
  2. Article first published online: 22 NOV 1999
  3. Manuscript Accepted: 13 SEP 1999
  4. Manuscript Received: 28 JUN 1999

Funded by

  • Assistance Publique-Hôpitaux de Paris

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Keywords:

  • pulmonary surfactant protein B (SP-B);
  • SFTPB;
  • hereditary SP-B deficiency;
  • pulmonary surfactant protein C (SP-C);
  • protein processing

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. Hum Mutat 14:502–509, 1999. © 1999 Wiley-Liss, Inc.

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