Population and Disease-Based Prevalence of the Common Mutations Associated With Surfactant Deficiency
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 mu...
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Published in | Pediatric research Vol. 63; no. 6; pp. 645 - 649 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Nature Publishing Group US
01.06.2008
Lippincott Williams & Wilkins |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Mr. Land’s current affiliation is the National Association for Public Health Statistics and Information Systems, Silver Spring, MD. Corresponding author: Aaron Hamvas, M.D., Division of Newborn Medicine, St. Louis Children’s Hospital, One Children’s Place, St. Louis, Missouri 63110, office: 314-454-6148, facsimile: 314-454-4633, hamvas@kids.wustl.edu |
ISSN: | 0031-3998 1530-0447 |
DOI: | 10.1203/PDR.0b013e31816fdbeb |