A leucine-to-proline substitution causes a defective alpha 1-antichymotrypsin allele associated with familial obstructive lung disease

Genomics. 1993 Sep;17(3):740-3. doi: 10.1006/geno.1993.1396.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • DNA Mutational Analysis
  • DNA, Complementary / genetics
  • Female
  • Humans
  • Lung Diseases, Obstructive / blood
  • Lung Diseases, Obstructive / genetics*
  • Male
  • Molecular Sequence Data
  • Pedigree
  • Point Mutation
  • Polymerase Chain Reaction
  • alpha 1-Antichymotrypsin / blood
  • alpha 1-Antichymotrypsin / genetics*


  • DNA, Complementary
  • alpha 1-Antichymotrypsin

Associated data

  • GENBANK/X68733
  • GENBANK/X68734
  • GENBANK/X68735
  • GENBANK/X68736
  • GENBANK/X68737