title: Novel mutations in the gene encoding ATP binding cassette protein member A3 (ABCA3) resulting in fatal neonatal lung disease.
abstract: OBJECTIVE
  To investigate whether intractable respiratory distress syndrome in three Norwegian term infants was due to mutations in the ABCA3 gene.
  
  
  METHODS
  The genes encoding SP-B (SFTPB), SP-C (SFTPC), and ABCA3 (ABCA3) were sequenced from the parents of one infant and two unrelated infants with fatal neonatal lung disease. Lung tissue was examined by histology, immunohistochemistry and electron microscopy.
  
  
  RESULTS
  Novel ABCA3 mutations were identified in each family. One patient had a phenotype differing from previous descriptions of this disease with an initial uneventful period. The diagnosis was established 19 years after death by analysing DNA material from the parents, with an ABCA3 mutation identified on one allele in each parent. The other two infants had more typical clinical courses with the onset of respiratory symptoms immediately after birth. ABCA3 mutations were identified on both alleles from these two infants, and electron microscopy of alveolar type 2 cells demonstrated abnormal lamellar body formation characteristic of this disorder.
  
  
  CONCLUSIONS
  ABCA3 mutations were the basis for lung disease in all three patients. Children with lung disease due to ABCA3 deficiency may not have symptoms at birth. The finding of five novel mutations indicates allelic heterogeneity for ABCA3 mutations within the Norwegian population.
authors: Department of Pediatric Research, Rikshospitalet-Radiumhospitalet Health Trust, University of Oslo, Oslo, Norway. o.d.saugstad@medisin.uio.no
authors: Ola D
authors: OD
authors: Saugstad
authors: Thor Willy Ruud
authors: TW
authors: Hansen
authors: Arild
authors: A
authors: Rønnestad
authors: Britt
authors: B
authors: Nakstad
authors: Per Arne
authors: PA
authors: Tølløfsrud
authors: Finn
authors: F
authors: Reinholt
authors: Aaron
authors: A
authors: Hamvas
authors: F Sessions
authors: FS
authors: Coles
authors: Michael
authors: M
authors: Dean
authors: Susan E
authors: SE
authors: Wert
authors: Jeffrey A
authors: JA
authors: Whitsett
authors: Lawrence M
authors: LM
authors: Nogee
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D009664:Norway; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics* / Q000473:pathology
chemical_list: C441524:ABCA3 protein, human; D018528:ATP-Binding Cassette Transporters