title: Large ABCA3 and SFTPC deletions resulting in lung disease.
abstract: BACKGROUND
  Mutations in genes encoding proteins important in the function and metabolism of pulmonary surfactant are recognized causes of lung disease. Clinical genetic testing is available for these disorders, but children with phenotypes consistent with surfactant dysfunction and no identifiable mutations in the known causative genes have been reported.
  
  
  OBJECTIVE
  To identify the mechanism(s) for lung disease in two children with the phenotype of surfactant dysfunction who had negative testing in clinical laboratories for gene mutations causing surfactant dysfunction.
  
  
  METHODS
  Amplicons spanning multiple exons of candidate genes were generated by polymerase chain reaction and sequenced.
  
  
  RESULTS
  A 4,335-base deletion that included all of exon 12 of the gene encoding member A3 of the adenosine triphosphate-binding cassette transporter was identified in a full-term infant with respiratory failure. A 333-base deletion involving part of exon 4 and the adjacent intron of the gene encoding surfactant protein C was identified in a child with interstitial lung disease.
  
  
  CONCLUSIONS
  Large deletions are a cause of surfactant dysfunction disorders and may need to be sought for specifically in children whose phenotypes suggest these syndromes but in whom clinical genetic testing is unrevealing.
authors.affiliation: 1 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Lindsay B
authors.initials: LB
authors.lastname: Henderson
authors.forename: Kristin
authors.initials: K
authors.lastname: Melton
authors.forename: Susan
authors.initials: S
authors.lastname: Wert
authors.forename: Jonathan
authors.initials: J
authors.lastname: Couriel
authors.forename: Andrew
authors.initials: A
authors.lastname: Bush
authors.forename: Michael
authors.initials: M
authors.lastname: Ashworth
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Nogee
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D008297:Male; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics*; D011663:Pulmonary Surfactants / Q000378:metabolism; D011859:Radiography; D012127:Respiratory Distress Syndrome, Newborn / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology
chemical_list: C441524:ABCA3 protein, human; D018528:ATP-Binding Cassette Transporters; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; C489679:SFTPC protein, human
references.citation: Pediatr Dev Pathol. 2009 Jul-Aug;12(4):253-74
references.pmid: 19220077
references.citation: Am J Respir Crit Care Med. 2005 Oct 15;172(8):1026-31
references.pmid: 15976379
references.citation: J Pediatr. 2010 Jul;157(1):62-8
references.pmid: 20304423
references.citation: Chest. 2013 Sep;144(3):794-804
references.pmid: 23430038
references.citation: J Histochem Cytochem. 2007 Jan;55(1):71-83
references.pmid: 16982851
references.citation: Horm Res Paediatr. 2012;77(3):146-51
references.pmid: 22488412
references.citation: J Pediatr. 2005 Mar;146(3):370-5
references.pmid: 15756222
references.citation: Am J Respir Crit Care Med. 2002 May 1;165(9):1322-8
references.pmid: 11991887
references.citation: N Engl J Med. 2001 Feb 22;344(8):573-9
references.pmid: 11207353
references.citation: Am J Respir Crit Care Med. 2006 Sep 1;174(5):590-8
references.pmid: 16728714
references.citation: J Pediatr. 2007 Jun;150(6):649-53, 653.e1
references.pmid: 17517255
references.citation: Arch Dis Child. 2013 Jul;98(7):490-5
references.pmid: 23625987
references.citation: Annu Rev Physiol. 2005;67:663-96
references.pmid: 15709974
references.citation: Pediatrics. 2011 May;127(5):e1347-51
references.pmid: 21464189
references.citation: J Med Genet. 2009 Jul;46(7):490-4
references.pmid: 19443464
references.citation: J Pediatr. 2009 Dec;155(6):854-859.e1
references.pmid: 19647838
references.citation: Acta Paediatr. 2007 Apr;96(4):516-20
references.pmid: 17391469
references.citation: Paediatr Respir Rev. 2011 Dec;12(4):223-9
references.pmid: 22018035