Complete absence of serum alpha-1-antitrypsin in conjunction with an apparently normal gene structure.

A family in which a Pinull allele for alpha-1-antitrypsin (A-1-AT) segregates has been studied in detail. Two homozygous sisters have no detectable A-1-AT in their serum as measured with the most sensitive methods currently available. Both have airways obstruction, and one has bullous emphysema. Heterozygotes for Pinull and the common normal allele PiM1 have half-normal serum concentrations of A-1-AT. A restriction enzyme analysis of chromosomal DNA of the two homozygotes and one heterozygote demonstrated the presence of an apparently complete structural gene for A-1-AT. Thus, the genetic defect in Pinull is not a complete or partial deletion of the structural gene. A base pair change that cannot be detected by the restriction enzymes used here, of course, cannot be excluded. Another possibility is a mutation outside the structural gene that affects the synthesis of the protein.