Population and disease-based prevalence of the common mutations associated with surfactant deficiency

Pediatr Res. 2008 Jun;63(6):645-9. doi: 10.1203/PDR.0b013e31816fdbeb.


The prevalence of the common mutations in the surfactant protein-B (121ins2), surfactant protein-C (I73T), and ATP-binding cassette member A3 (E292V) genes in population-based or case-control cohorts of newborn respiratory distress syndrome (RDS) is unknown. We determined the frequencies of these mutations in ethnically diverse population and disease-based cohorts using restriction enzyme analysis (121ins2 and E292V) and a 5' nuclease assay (I73T) in DNA samples from population-based cohorts in Missouri, Norway, South Korea, and South Africa, and from a case-control cohort of newborns with and without RDS (n = 420). We resequenced the ATP-binding cassette member A3 gene (ABCA3) in E292V carriers and computationally inferred ABCA3 haplotypes. The population-based frequencies of 121ins2, E292V, and I73T were rare (<0.4%). E292V was present in 3.8% of newborns with RDS, a 10-fold greater prevalence than in the Missouri cohort (p < 0.001). We did not identify other loss of function mutations in ABCA3 among patients with E292V that would account for their RDS. E292V occurred on a unique haplotype that was derived from a recombination of two common ABCA3 haplotypes. E292V was over-represented in newborns with RDS suggesting that E292V or its unique haplotype impart increased genetic risk for RDS.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / metabolism
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Infant
  • Infant, Newborn
  • Korea
  • Male
  • Missouri
  • Mutation*
  • Norway
  • Population Surveillance
  • Pulmonary Surfactant-Associated Protein B / deficiency
  • Pulmonary Surfactant-Associated Protein B / genetics*
  • Pulmonary Surfactant-Associated Protein C / deficiency
  • Pulmonary Surfactant-Associated Protein C / genetics*
  • Respiratory Distress Syndrome, Newborn / genetics*
  • Respiratory Distress Syndrome, Newborn / metabolism
  • Risk Factors
  • South Africa


  • ABCA3 protein, human
  • ATP-Binding Cassette Transporters
  • Pulmonary Surfactant-Associated Protein B
  • Pulmonary Surfactant-Associated Protein C
  • SFTPC protein, human