title: Genetic mutations in surfactant protein C are a rare cause of sporadic cases of IPF.
abstract: BACKGROUND
  While idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease, the aetiology of IPF is poorly understood. Familial cases of pulmonary fibrosis suggest a genetic basis for some forms of the disease. Recent reports have linked genetic mutations in surfactant protein C (SFTPC) with familial forms of pulmonary fibrosis, including one large family in which a number of family members were diagnosed with usual interstitial pneumonitis (UIP), the pathological correlate to IPF. Because of this finding in familial cases of pulmonary fibrosis, we searched for SFTPC mutations in a cohort of sporadic cases of UIP and non-specific interstitial pneumonitis (NSIP).
  
  
  METHODS
  The gene for SFTPC was sequenced in 89 patients diagnosed with UIP, 46 patients with NSIP, and 104 normal controls.
  
  
  RESULTS
  Ten single nucleotide polymorphisms in the SFTPC sequence were found in IPF patients and not in controls. Only one of these created an exonic change resulting in a change in amino acid sequence. In this case, a T to C substitution resulted in a change in amino acid 73 of the precursor protein from isoleucine to threonine. Of the remaining polymorphisms, one was in the 5' UTR, two were exonic without predicted amino acid sequence changes, and six were intronic. One intronic mutation suggested a potential enhancement of a splicing site.
  
  
  CONCLUSIONS
  Mutations in SFTPC are identified infrequently in this patient population. These findings indicate that SFTPC mutations do not contribute to the pathogenesis of IPF in the majority of sporadic cases.
authors.affiliation: Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2650, USA.
authors.forename: W E
authors.initials: WE
authors.lastname: Lawson
authors.forename: S W
authors.initials: SW
authors.lastname: Grant
authors.forename: V
authors.initials: V
authors.lastname: Ambrosini
authors.forename: K E
authors.initials: KE
authors.lastname: Womble
authors.forename: E P
authors.initials: EP
authors.lastname: Dawson
authors.forename: K B
authors.initials: KB
authors.lastname: Lane
authors.forename: C
authors.initials: C
authors.lastname: Markin
authors.forename: E
authors.initials: E
authors.lastname: Renzoni
authors.forename: P
authors.initials: P
authors.lastname: Lympany
authors.forename: A Q
authors.initials: AQ
authors.lastname: Thomas
authors.forename: J
authors.initials: J
authors.lastname: Roldan
authors.forename: T A
authors.initials: TA
authors.lastname: Scott
authors.forename: T S
authors.initials: TS
authors.lastname: Blackwell
authors.forename: J A
authors.initials: JA
authors.lastname: Phillips
authors.forename: J E
authors.initials: JE
authors.lastname: Loyd
authors.forename: R M
authors.initials: RM
authors.lastname: du Bois
mesh_terms: D005260:Female; D005784:Gene Amplification; D006579:Heterozygote; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics*
chemical_list: D037721:Pulmonary Surfactant-Associated Protein C