A LEUCINE-TO-PROLINE SUBSTITUTION CAUSES A DEFECTIVE ALPHA(1)-ANTICHYMOTRYPSIN ALLELE ASSOCIATED WITH FAMILIAL OBSTRUCTIVE LUNG-DISEASE

Using denaturing gradient gel electrophoresis and direct sequencing of amplified genomic DNA, we have identified two defective mutants of the human α1-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. © 1993 Academic Press, Inc.