title: Identification of early interstitial lung disease in an individual with genetic variations in ABCA3 and SFTPC.
abstract: A man with usual interstitial pneumonia (age of onset 58 years) was previously found to have an Ile73Thr (I73T) surfactant protein C (SFTPC) mutation. Genomic DNA from the individual and two daughters (aged 39 and 43 years) was sequenced for the I73T mutation and variations in ATP-binding cassette A3 (ABCA3). All three had the I73T SFTPC mutation. The father and one daughter (aged 39 years) also had a transversion encoding an Asp123Asn (D123N) substitution in ABCA3. The daughters were evaluated by pulmonary function testing and high-resolution CT (HRCT). Neither daughter had evidence of disease, except for focal subpleural septal thickening on HRCT scan in one daughter (aged 39 years). This daughter underwent bronchoscopy with transbronchial biopsies revealing interstitial fibrotic remodeling. These findings demonstrate that subclinical fibrotic changes may be present in family members of patients with SFTPC mutation-associated interstitial lung disease and suggest that ABCA3 variants could affect disease pathogenesis.
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, T-1218 MCN, Nashville, TN 37232-2650, USA.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Crossno
authors.forename: Vasiliy V
authors.initials: VV
authors.lastname: Polosukhin
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Blackwell
authors.forename: Joyce E
authors.initials: JE
authors.lastname: Johnson
authors.forename: Cheryl
authors.initials: C
authors.lastname: Markin
authors.forename: Paul E
authors.initials: PE
authors.lastname: Moore
authors.forename: John A
authors.initials: JA
authors.lastname: Worrell
authors.forename: Mildred T
authors.initials: MT
authors.lastname: Stahlman
authors.forename: John A
authors.initials: JA
authors.lastname: Phillips
authors.forename: James E
authors.initials: JE
authors.lastname: Loyd
authors.forename: Joy D
authors.initials: JD
authors.lastname: Cogan
authors.forename: William E
authors.initials: WE
authors.lastname: Lawson
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D005260:Female; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics*
chemical_list: C441524:ABCA3 protein, human; D018528:ATP-Binding Cassette Transporters; D037721:Pulmonary Surfactant-Associated Protein C; C489679:SFTPC protein, human