Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Apr;93(4):1860–1863. doi: 10.1172/JCI117173

A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds.

L M Nogee 1, G Garnier 1, H C Dietz 1, L Singer 1, A M Murphy 1, D E deMello 1, H R Colten 1
PMCID: PMC294267  PMID: 8163685

Abstract

To determine the molecular defect accounting for the deficiency of pulmonary surfactant protein B (SP-B) in full-term neonates who died from respiratory failure associated with alveolar proteinosis, the sequence of the SP-B transcript in affected infants was ascertained. A frameshift mutation consisting of a substitution of GAA for C in codon 121 of the SP-B cDNA was identified. The three affected infants in the index family were homozygous for this mutation, which segregated in a fashion consistent with autosomal recessive inheritance of disease. The same mutation was found in two other unrelated infants who died from alveolar proteinosis, one of whom was also homozygous, and in the parents of an additional unrelated, affected infant, but was not observed in 50 control subjects. We conclude that this mutation is responsible for SP-B deficiency and neonatal alveolar proteinosis in multiple families and speculate that the disorder is more common than was recognized previously.

Full text

PDF
1860

Images in this article

1861Image
on p.1861
1861Image
on p.1861
1861Image
on p.1861
1862Image
on p.1862

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baserga S. J., Benz E. J., Jr Nonsense mutations in the human beta-globin gene affect mRNA metabolism. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2056–2060. doi: 10.1073/pnas.85.7.2056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Belgrader P., Cheng J., Maquat L. E. Evidence to implicate translation by ribosomes in the mechanism by which nonsense codons reduce the nuclear level of human triosephosphate isomerase mRNA. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):482–486. doi: 10.1073/pnas.90.2.482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cheng J., Maquat L. E. Nonsense codons can reduce the abundance of nuclear mRNA without affecting the abundance of pre-mRNA or the half-life of cytoplasmic mRNA. Mol Cell Biol. 1993 Mar;13(3):1892–1902. doi: 10.1128/mcb.13.3.1892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  5. Coleman M., Dehner L. P., Sibley R. K., Burke B. A., L'Heureux P. R., Thompson T. R. Pulmonary alveolar proteinosis: an uncommon cause of chronic neonatal respiratory distress. Am Rev Respir Dis. 1980 Mar;121(3):583–586. doi: 10.1164/arrd.1980.121.3.583. [DOI] [PubMed] [Google Scholar]
  6. Dietz H. C., Valle D., Francomano C. A., Kendzior R. J., Jr, Pyeritz R. E., Cutting G. R. The skipping of constitutive exons in vivo induced by nonsense mutations. Science. 1993 Jan 29;259(5095):680–683. doi: 10.1126/science.8430317. [DOI] [PubMed] [Google Scholar]
  7. Farrell P. M., Avery M. E. Hyaline membrane disease. Am Rev Respir Dis. 1975 May;111(5):657–688. doi: 10.1164/arrd.1975.111.5.657. [DOI] [PubMed] [Google Scholar]
  8. Fisher C. W., Fisher C. R., Chuang J. L., Lau K. S., Chuang D. T., Cox R. P. Occurrence of a 2-bp (AT) deletion allele and a nonsense (G-to-T) mutant allele at the E2 (DBT) locus of six patients with maple syrup urine disease: multiple-exon skipping as a secondary effect of the mutations. Am J Hum Genet. 1993 Feb;52(2):414–424. [PMC free article] [PubMed] [Google Scholar]
  9. Glasser S. W., Korfhagen T. R., Weaver T., Pilot-Matias T., Fox J. L., Whitsett J. A. cDNA and deduced amino acid sequence of human pulmonary surfactant-associated proteolipid SPL(Phe). Proc Natl Acad Sci U S A. 1987 Jun;84(12):4007–4011. doi: 10.1073/pnas.84.12.4007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hamosh A., Trapnell B. C., Zeitlin P. L., Montrose-Rafizadeh C., Rosenstein B. J., Crystal R. G., Cutting G. R. Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and W1316X in respiratory epithelial cells of patients with cystic fibrosis. J Clin Invest. 1991 Dec;88(6):1880–1885. doi: 10.1172/JCI115510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jacobs K. A., Phelps D. S., Steinbrink R., Fisch J., Kriz R., Mitsock L., Dougherty J. P., Taeusch H. W., Floros J. Isolation of a cDNA clone encoding a high molecular weight precursor to a 6-kDa pulmonary surfactant-associated protein. J Biol Chem. 1987 Jul 15;262(20):9808–9811. [PubMed] [Google Scholar]
  12. Kadowaki T., Kadowaki H., Rechler M. M., Serrano-Rios M., Roth J., Gorden P., Taylor S. I. Five mutant alleles of the insulin receptor gene in patients with genetic forms of insulin resistance. J Clin Invest. 1990 Jul;86(1):254–264. doi: 10.1172/JCI114693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Knight D. P., Knight J. A. Pulmonary alveolar proteinosis in the newborn. Arch Pathol Lab Med. 1985 Jun;109(6):529–531. [PubMed] [Google Scholar]
  14. Moulton S. L., Krous H. F., Merritt T. A., Odell R. M., Gangitano E., Cornish J. D. Congenital pulmonary alveolar proteinosis: failure of treatment with extracorporeal life support. J Pediatr. 1992 Feb;120(2 Pt 1):297–302. doi: 10.1016/s0022-3476(05)80448-2. [DOI] [PubMed] [Google Scholar]
  15. Nogee L. M., de Mello D. E., Dehner L. P., Colten H. R. Brief report: deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis. N Engl J Med. 1993 Feb 11;328(6):406–410. doi: 10.1056/NEJM199302113280606. [DOI] [PubMed] [Google Scholar]
  16. Pilot-Matias T. J., Kister S. E., Fox J. L., Kropp K., Glasser S. W., Whitsett J. A. Structure and organization of the gene encoding human pulmonary surfactant proteolipid SP-B. DNA. 1989 Mar;8(2):75–86. doi: 10.1089/dna.1.1989.8.75. [DOI] [PubMed] [Google Scholar]
  17. Revak S. D., Merritt T. A., Degryse E., Stefani L., Courtney M., Hallman M., Cochrane C. G. Use of human surfactant low molecular weight apoproteins in the reconstitution of surfactant biologic activity. J Clin Invest. 1988 Mar;81(3):826–833. doi: 10.1172/JCI113391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rogers B. B., Alpert L. C., Hine E. A., Buffone G. J. Analysis of DNA in fresh and fixed tissue by the polymerase chain reaction. Am J Pathol. 1990 Mar;136(3):541–548. [PMC free article] [PubMed] [Google Scholar]
  19. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Satoh K., Nukiwa T., Brantly M., Garver R. I., Jr, Hofker M., Courtney M., Crystal R. G. Emphysema associated with complete absence of alpha 1- antitrypsin in serum and the homozygous inheritance [corrected] of a stop codon in an alpha 1-antitrypsin-coding exon. Am J Hum Genet. 1988 Jan;42(1):77–83. [PMC free article] [PubMed] [Google Scholar]
  21. Schumacher R. E., Marrogi A. J., Heidelberger K. P. Pulmonary alveolar proteinosis in a newborn. Pediatr Pulmonol. 1989;7(3):178–182. doi: 10.1002/ppul.1950070312. [DOI] [PubMed] [Google Scholar]
  22. Todd S., Naylor S. L. Dinucleotide repeat polymorphism in the human surfactant-associated protein 3 gene (SFTP3). Nucleic Acids Res. 1991 Jul 11;19(13):3756–3756. [PMC free article] [PubMed] [Google Scholar]
  23. Urlaub G., Mitchell P. J., Ciudad C. J., Chasin L. A. Nonsense mutations in the dihydrofolate reductase gene affect RNA processing. Mol Cell Biol. 1989 Jul;9(7):2868–2880. doi: 10.1128/mcb.9.7.2868. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES