Abstract
Background: ABCA3 is an ATP Binding Cassette protein localized to the limiting membrane of lamellar bodies in alveolar Type II cells. Recessive mutations in ABCA3 disrupt surfactant composition and function and cause lethal respiratory distress in newborns. A valine for glutamic acid substitution at codon 292 (E292V) has been found in unrelated individuals with chronic respiratory insufficiency.
Objective: To determine the prevalence of the E292V variant in infants with and without RDS. Design/Methods: We obtained genomic DNA and clinical data from an unselected cohort of newborns with RDS (RDS, n=125, gestational age [GA] 31±5 wks), newborns with RDS referred for evaluation of familial or atypical RDS (REF, n=56, GA 34±5 wks), and normal newborns (noRDS, n=167, GA 39±2 wks). We amplified a 637 base pair product that included codon 292 and subjected amplicons to BsrG1 restriction analysis and agarose gel electrophoresis.
Results: Excluding 1 each of concordant twins in the REF and noRDS groups, 3 RDS (2.4%), 5 REF (9.1%), and 2 noRDS (1.2%) infants were heterozygous for E292V (P=0.009). Males and females were equally represented. One infant with E292V in the noRDS group was Black, all others with E292V were White. Symptomatic infants (REF+RDS) with E292V were more mature than those without E292V (35±3 vs 32±5 wks, P=0.007). Duration of mechanical ventilation, and need for supplemental oxygen were not significantly different. Infants with RDS and E292V developed pneumothoraces more frequently (78%) than infants with RDS but without E292V (9%) (P<0.001). Six infants had resolution of symptoms within 1 month of birth; the noRDS individuals with E292V remained asymptomatic.
Conclusions: The E292V variant in ABCA3 is significantly more prevalent in infants with RDS than in asymptomatic controls. Patients heterozygous for E292V come to clinical attention by presenting with RDS that is more severe than anticipated for gestational age. E292V may be a genetic influence for the risk and severity of RDS.
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Garmany, T., Bullard, J., Heins, H. et al. 166 The E292V Variant in ABCA3 is Over-Represented in Newborns with Respiratory Distress Syndrome (RDS). Pediatr Res 58, 383 (2005). https://doi.org/10.1203/00006450-200508000-00195
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DOI: https://doi.org/10.1203/00006450-200508000-00195