Genetic variants of alpha-1-antitrypsin (AAT)

Authors

  • Glovanna Fabbretti,

    Corresponding author
    1. Department of Pathology and Molecular Genetics, Children's Hospital G. Gaslini Institute, Genoa and Department of Pathology University of Cagliari, Italy
      Department of Pathology, G. Gaslini Institue, L.go G. Gaslini. 5, Genova-Quarto 16148, Italy
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  • Censolate Sergl,

    1. Department of Pathology and Molecular Genetics, Children's Hospital G. Gaslini Institute, Genoa and Department of Pathology University of Cagliari, Italy
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  • Glacomo Consales,

    1. Department of Pathology and Molecular Genetics, Children's Hospital G. Gaslini Institute, Genoa and Department of Pathology University of Cagliari, Italy
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  • Gavino Faa,

    1. Department of Pathology and Molecular Genetics, Children's Hospital G. Gaslini Institute, Genoa and Department of Pathology University of Cagliari, Italy
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  • Massimo Brisigotti,

    1. Department of Pathology and Molecular Genetics, Children's Hospital G. Gaslini Institute, Genoa and Department of Pathology University of Cagliari, Italy
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  • Glovannl Romeo,

    1. Department of Pathology and Molecular Genetics, Children's Hospital G. Gaslini Institute, Genoa and Department of Pathology University of Cagliari, Italy
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  • Francesco Callea

    1. Department of Pathology and Molecular Genetics, Children's Hospital G. Gaslini Institute, Genoa and Department of Pathology University of Cagliari, Italy
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Errata

This article is corrected by:

  1. Errata: Corrigendum Volume 33, Issue 1, 164, Article first published online: 10 December 2012

Department of Pathology, G. Gaslini Institue, L.go G. Gaslini. 5, Genova-Quarto 16148, Italy

Abstract

Abstract: This paper reviews the genetic variants of alpha-1-antitrypsin (AAT) which have been sequenced with special emphasis on the s.c. deficiency variants. These result in AAT low plasma levels via three main mechanisms: 1) intracellular storage; 2) intracellular degradation; 3) lack of synthesis. Intracellular storage occurs with the classical Z variant and with a few variants called M-like, because of their isoelectric focusing (IF) pattern. The storage phenomen causes liver damage and can be demonstrated at both light and electron microscopic level with the help of immuno-histochemistry. We report a new deficiency variant of AAT (M-Cagliari) characterized by very low plasma levels, massive storage of AAT and liver cirrhosis. By using immunohistochemical techniques and DNA analysis we could demonstrate that M-Cagliari has antigenic and genetic properties other than the Z AAT.

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