Summary
Two rare α1-antitrypsin variants, Pi I and Plowell, originally defined at the protein level through isoelectric focusing, were characterized at the DNA level by the polymerase chain reaction and direct sequencing. The I variant was confirmed in one individual and three independent families to result from a CGC(Arg) to TGC(Cys) transition at codon 39, within exon II. In our population, the Pi I variant might be more common than expected. The Plowell allele was shown in one M3P heterozygous individual to be due to a GAT(Asp) to GTT (Val) change at codon 256, in agreement with a previous study based on hybridization with allele-specific oligonucleotides.
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References
Arnaud P, Chapuis-Cellier C, Vittoz P, Fudemberg HH, Genetic polymorphism of serum alpha-1-protease inhibitor (alpha-1-antitrypsin): Pi I, a deficient allele of the Pi system. J Lab Clin Med 92:177, 1978
Brantly M, Nukiwa T, Crystal RG, Molecular basis of alpha-1-antitrypsin deficiency. Am J Med 84 [Suppl 6A]:13, 1988
Cox DW, α1-antitrypsin deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 2409–2437, 1989
Crystal RG, The α1-antitrypsin gene and its deficiency states. Trends in Genetics 5:411, 1989
Crystal RG, Brantly ML, Hubbard RC, Curiel DT, States DJ, Holmes MD, The alpha-1-antitrypsin gene and its mutations. Chest 95:196, 1989.
Faber JP, Weidinger S, Goedde HW, Olek K, The deficient alpha-1-antitrypsin phenotype Pi P is associated with am A-to-T transversion in exon III of the gene. Am J Hum Genet 45:161, 1989
Fagerhol MK, Hauge HE, The Pi phenotype MP. Discovery of a ninth allele belonging to the system of inherited variants of serum α1-antitrypsin. Vox Sang 15:396, 1968
Graham A, Kalsheker NA, Newton CR, Bamforth FJ, Powell SJ, Markham AF, Molecular characterisation of three alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) nullcardiff (Asp256→Val); PiMmalton (Phe51→deletion) and PiI (Arg39→Cys), Hum Genet 84:55, 1989
Hildesheim J, Kinsley G, Bissel M, Pierce J, Brantly M, α1-antitrypsin Pduarte: heterogeneity of P-family alleles resulting from gene mutations on different normal background alleles. Proceedings of the 8th International Congress on Human Genetics, 6–11 October 1991, Washington, Am J Hum Genet 49:2797, 1991
Long GL, Chandra T, Woo SLC, Davie EW, Kurachi K, Complete sequence of the cDNA for human α1-antitrypsin and the gene for the S variant. Biochemistry 23:4828, 1984
Nowicki ML, Freler EF, Improved method for identifying α1-antitrypsin Pi M subtypes by isoelectric focusing in agarose. Clin Chem 36:1815, 1990
Sambrook J, Fritsch EF, Maniatis T, Molecular cloning—a laboratory manual. Cold Spring Harbor Laboratory Press. 2nd edition, 1989
Weidinger S, Jeppsson JO, Genetic study of the deficient α1-antitrypsin variant Pi P. Proceedings of the 7th International congress on Human Genetics, 22–26 September 1986, Berlin, Abstract Book, p. 435, 1986.
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Seri, M., Magi, B., Cellesi, C. et al. Molecular characterization of the P and I variants of α1-antitrypsin. Int J Clin Lab Res 22, 119–121 (1992). https://doi.org/10.1007/BF02591409
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DOI: https://doi.org/10.1007/BF02591409