title: A leucine-to-proline substitution causes a defective alpha 1-antichymotrypsin allele associated with familial obstructive lung disease.
abstract: Using denaturing gradient gel electrophoresis and direct sequencing of amplified genomic DNA, we have identified two defective mutants of the human alpha 1-antichymotrypsin (ACT) gene associated with chronic obstructive pulmonary disease (COPD). A leucine 55-to-proline substitution causing a defective ACT allele (Bochum-1) was observed in a family with COPD in three subsequent generations. Another mutation, proline 229-to-alanine (Bonn-1), was associated with ACT serum deficiency in four patients with a positive family history. These mutations were not detected among 100 healthy control subjects, suggesting a possible pathogenetic role of ACT gene defects in a subset of patients with COPD.
authors.affiliation: University Medical Clinic, Bergmannsheil Hospital, University of Bochum, Federal Republic of Germany.
authors.forename: W
authors.initials: W
authors.lastname: Poller
authors.forename: J P
authors.initials: JP
authors.lastname: Faber
authors.forename: S
authors.initials: S
authors.lastname: Weidinger
authors.forename: K
authors.initials: K
authors.lastname: Tief
authors.forename: S
authors.initials: S
authors.lastname: Scholz
authors.forename: M
authors.initials: M
authors.lastname: Fischer
authors.forename: K
authors.initials: K
authors.lastname: Olek
authors.forename: M
authors.initials: M
authors.lastname: Kirchgesser
authors.forename: H H
authors.initials: HH
authors.lastname: Heidtmann
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000097:blood / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D000514:alpha 1-Antichymotrypsin / Q000097:blood / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D000514:alpha 1-Antichymotrypsin