title: Nonspecific interstitial pneumonia and usual interstitial pneumonia with mutation in surfactant protein C in familial pulmonary fibrosis.
abstract: Nonspecific interstitial pneumonia, a recently described form of idiopathic interstitial pneumonia, is characterized by uniform involvement of the alveolar septae with interstitial inflammation and variable amounts of fibrosis. Histological observations differentiate nonspecific interstitial pneumonia from usual interstitial pneumonia and clinically, patients with a nonspecific interstitial pneumonia pattern show better prognosis than those with usual interstitial pneumonia. We have genetically analyzed a family with a history of usual interstitial pneumonia. Most of the patients presented as adults and their biopsies showed a pattern consistent with usual interstitial pneumonia. However, three family members presented in early childhood and their biopsies revealed a nonspecific interstitial pneumonia pattern. The inheritance pattern of usual interstitial pneumonia is consistent with autosomal dominant inheritance with variable expression. DNA sequence analyses of the surfactant protein C gene in children with nonspecific interstitial pneumonia and adults with usual interstitial pneumonia exhibit a common heterozygous mutation located in exon 5. The mutation causes a Leu188 to Gln188 change in the carboxy-terminal region of prosurfactant protein C, possibly affecting peptide processing. These observations suggest that individuals with this particular mutation in surfactant protein C gene might be at increased risk of interstitial lung disease of variety of types.
authors.affiliation: Department of Pathology, University of Saskatchewan, Saskatoon, SK, Canada. rajni.chibbar@saskatoonhealthregion.ca
authors.forename: Rajni
authors.initials: R
authors.lastname: Chibbar
authors.forename: Francis
authors.initials: F
authors.lastname: Shih
authors.forename: Monica
authors.initials: M
authors.lastname: Baga
authors.forename: Emina
authors.initials: E
authors.lastname: Torlakovic
authors.forename: Kumar
authors.initials: K
authors.lastname: Ramlall
authors.forename: Robert
authors.initials: R
authors.lastname: Skomro
authors.forename: Donald W
authors.initials: DW
authors.lastname: Cockcroft
authors.forename: Edmond G
authors.initials: EG
authors.lastname: Lemire
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D007223:Infant; D017563:Lung Diseases, Interstitial / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000473:pathology*; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics*
chemical_list: D037721:Pulmonary Surfactant-Associated Protein C; D004247:DNA