Population and Disease-Based Prevalence of the Common Mutations Associated With Surfactant Deficiency

• Published in: Pediatric research Vol. 63; no. 6; pp. 645 - 649
• Main Authors: Garmany, Tami H, Wambach, Jennifer A, Heins, Hillary B, Watkins-Torry, Julie M, Wegner, Daniel J, Bennet, Kate, An, Ping, Land, Garland, Saugstad, Ola D, Henderson, Howard, Nogee, Lawrence M, Cole, F Sessions, Hamvas, Aaron
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.06.2008; Lippincott Williams & Wilkins
• Subjects: ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Biological and medical sciences; Case-Control Studies; Epidemiology; Female; Gene Frequency; General aspects; Genetic Predisposition to Disease; Haplotypes; Humans; Infant; Infant, Newborn; Korea; Male; Medical sciences; Medicine; Medicine & Public Health; Miscellaneous; Missouri; Mutation; Norway; Pediatric Surgery; Pediatrics; Population Surveillance; Public health. Hygiene; Public health. Hygiene-occupational medicine; 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; translational-investigation; Pediatrics; Association; Prevalence; Disease; Respiratory disease; Lung surfactant deficiency; Genetics; Population; Mutation; Epidemiology; Public health
• ISSN: 0031-3998; 1530-0447
• 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.