Summary
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 NullNewport 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.
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Graham, A., Kalsheker, N.A., Bamforth, F.J. et al. Molecular characterisation of two alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) NullNewport (Gly115→Ser) and (Pi) Z Wrexham (Ser−19→Leu). Hum Genet 85, 537–540 (1990). https://doi.org/10.1007/BF00194233
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DOI: https://doi.org/10.1007/BF00194233