title: Molecular characterisation of three alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) nullcardiff (Asp256----Val); PiMmalton (Phe51----deletion) and PiI (Arg39----Cys).
abstract: Three mutations causing alpha-1-antitrypsin deficiency have been identified by gene amplification and direct DNA sequencing. In the Pi (proteinase-inhibitor) nullcardiff gene, the codon for aspartate at position 256 has mutated to encode valine. In PiMmalton and Pi I, the respective mutations are the deletion of the codon for a phenylalanine residue at position 51 or 52, and a single base substitution resulting in arginine being replaced by cysteine at position 39. Examination of the protein tertiary structure suggests that all of these mutations are likely to result in folding abnormalities that may explain the deficiency states.
authors.affiliation: ICI Diagnostics, Gadbrook Park, Northwich, Cheshire, UK.
authors.forename: A
authors.initials: A
authors.lastname: Graham
authors.forename: N A
authors.initials: NA
authors.lastname: Kalsheker
authors.forename: C R
authors.initials: CR
authors.lastname: Newton
authors.forename: F J
authors.initials: FJ
authors.lastname: Bamforth
authors.forename: S J
authors.initials: SJ
authors.lastname: Powell
authors.forename: A F
authors.initials: AF
authors.lastname: Markham
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine; D001224:Aspartic Acid; D001483:Base Sequence; D002872:Chromosome Deletion; D003545:Cysteine; D005796:Genes; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010649:Phenylalanine; D014633:Valine; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency
chemical_list: D015345:Oligonucleotide Probes; D000515:alpha 1-Antitrypsin; D001224:Aspartic Acid; D010649:Phenylalanine; D001120:Arginine; D014633:Valine; D003545:Cysteine