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

Tami H. Garmany, Jennifer A. Wambach, Hillary B. Heins, Julie M. Watkins-Torry, Daniel J. Wegner, Kate Bennet, Ping An, Garland Land, Ola D. Saugstad, Howard Henderson, Lawrence M. Nogee, F. Sessions Cole, Aaron Hamvas

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


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.

Original languageEnglish
Pages (from-to)645-649
Number of pages5
JournalPediatric research
Issue number6
StatePublished - Jun 2008


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