title: Molecular characterisation of two alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) Null(Newport) (Gly115----Ser) and (Pi) Z Wrexham (Ser-19----Leu).
abstract: Two single point mutations in the alpha-1-antitrypsin gene, resulting in AAT deficiency, have been characterised in heterozygotes by DNA amplification and direct sequencing. The mutations result in amino acid substitutions, Gly115----Ser and Ser-19----Leu, in the leader sequence, respectively, and have been designated Pi Null(Newport) and Pi Z Wrexham. In the two families studied the mutations occur on chromosomes which also carry the common mutation causing Z deficiency. Individuals with such a deficiency are, therefore, compound heterozygotes. It is not known if these particular mutations would only cause a mild form of AAT deficiency in the absence of the Z mutation as they do not appear to cause predictable folding abnormalities. They do, however, result in severe deficiency when the Z mutation occurs in the same gene.
authors.affiliation: ICI Pharmaceuticals, Macclesfield, Cheshire, UK.
authors.forename: A
authors.initials: A
authors.lastname: Graham
authors.forename: N A
authors.initials: NA
authors.lastname: Kalsheker
authors.forename: F J
authors.initials: FJ
authors.lastname: Bamforth
authors.forename: C R
authors.initials: CR
authors.lastname: Newton
authors.forename: A F
authors.initials: AF
authors.lastname: Markham
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005784:Gene Amplification; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency
chemical_list: D000515:alpha 1-Antitrypsin