title: A common mutation in the surfactant protein C gene associated with lung disease.
abstract: OBJECTIVE
  To determine the contribution of the surfactant protein C (SP-C) I73T mutation to lung disease.
  
  
  METHODS
  Genomic DNA was obtained from 116 children with interstitial lung disease (ILD) or chronic lung disease of unclear cause and from 166 control subjects and was screened for the I73T mutation using an allele-specific polymerase chain reaction assay.
  
  
  RESULTS
  The I73T mutation was found on 7 of 232 SP-C alleles from 7 unrelated children with ILD but was not found on 332 control SP-C alleles ( P < .01, Fisher exact test). The I73T mutation segregated with lung disease in one kindred with familial ILD. The I73T mutation was found in an asymptomatic parent from two different families with affected children consistent with variable penetrance, but it was not found in either asymptomatic parent of two other unrelated affected children consistent with a de novo mutation. Analysis of single nucleotide polymorphisms indicated diverse genetic backgrounds of the I73T alleles. Immunohistochemical analysis of lung tissue from an infant with the I73T mutation demonstrated normal staining patterns for proSP-B, SP-B, and proSP-C.
  
  
  CONCLUSIONS
  These findings support the hypothesis that the I73T mutation predisposes to or causes lung disease.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: H Scott
authors.initials: HS
authors.lastname: Cameron
authors.forename: Marco
authors.initials: M
authors.lastname: Somaschini
authors.forename: Paola
authors.initials: P
authors.lastname: Carrera
authors.forename: Aaron
authors.initials: A
authors.lastname: Hamvas
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Whitsett
authors.forename: Susan E
authors.initials: SE
authors.lastname: Wert
authors.forename: Gail
authors.initials: G
authors.lastname: Deutsch
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Nogee
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000235:genetics*; D017563:Lung Diseases, Interstitial / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D037721:Pulmonary Surfactant-Associated Protein C