Characterization of the molecular basis of the α1-antitrypsin F allele

H. Okayama, M. Brantly, M. Holmes, Ronald Crystal

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α1-Antitrypsin (α1AT), the major serum inhibitor of neutrophil elastase, is a highly polymorphic serum protein associated with characteristic isoelectric-focusing (IEF) patterns for most variants. To characterize the molecular basis of the anodal F variant, the DNA sequence of the coding exons of an FZ individual was determined. The F allele differed from the normal M1(Val213) α1AT allele by a single nucleotide transversion of cytosine to thymidine, which results in the amino acid substitution Arg223 CGT→Cys TGT. Inheritance of the F mutation was confirmed by family analysis using allele-specific amplification. In the context that the normal α1AT molecule has only one cysteine residue, a mutation resulting in the addition of a second cysteine may influence the three-dimensional form of the protein and/or permit interaction with other plasma proteins with free-SH groups and may be responsible for the observation that the major F α1AT bands often migrate as doublets in IEF gels.

Original languageEnglish
Pages (from-to)1154-1158
Number of pages5
JournalAmerican Journal of Human Genetics
Issue number6
Publication statusPublished - 28 Jun 1991
Externally publishedYes


ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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