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A New SERPINA-1 Missense Mutation Associated with Alpha-1 Antitrypsin Deficiency and Bronchiectasis

Lung volume 195, pages 679–682 (2017)Cite this article

Abstract

Alpha-1-antitrypsin deficiency (AATD) is a genetic condition caused by SERPINA1 mutations, which culminates into lower protease inhibitor activity in the serum and predisposes to emphysema. Clinical manifestations of AATD are often associated to ZZ (p.Glu342Lys) and SZ (p.Glu264Val) genotypes and less frequently to rare deficiency or null alleles in heterozygous and homozygous states. We report a case of a 52-year-old woman with bronchiectasis without other potential causes other than an electrophoresis that showed a decrease of alpha-1 globin band and AAT levels below the normal value (78 mg/dl; v.n. 90–200 mg/dl). No S or Z mutation was identified, but sequencing analysis found a novel missense variant Ile74Asn (c.221T > A) in heterozygous state on an M3 allele (Glu400Asp) in the exon 2 of the SERPINA-1gene, probably leading to a dysfunctional protein. This mutation has never been previously identified, and it is interesting to note the association with bronchiectasis in the absence of emphysema.

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Author notes

  1. G. E. Carpagnano and R. Santacroce have contributed equally to the paper.

Authors and Affiliations

  1. Department of Medical and Surgical Sciences, Institute of Respiratory Diseases, University of Foggia, Foggia, Italy

    G. E. Carpagnano, G. A. Palmiotti, E. Giuffreda, M. P. Foschino Barbaro & D. Lacedonia

  2. Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy

    R. Santacroce, A. Leccese & M. Margaglione

  3. Department of Pathophysiology and Transplantation, Cardio-Thoracic Unit and Adult Cystic Fibrosis Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

    S. Aliberti

Authors
  1. G. E. Carpagnano
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  2. R. Santacroce
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  3. G. A. Palmiotti
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  4. A. Leccese
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  5. E. Giuffreda
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  6. M. Margaglione
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  7. M. P. Foschino Barbaro
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  8. S. Aliberti
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  9. D. Lacedonia
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Corresponding author

Correspondence to G. A. Palmiotti.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Carpagnano, G.E., Santacroce, R., Palmiotti, G.A. et al. A New SERPINA-1 Missense Mutation Associated with Alpha-1 Antitrypsin Deficiency and Bronchiectasis. Lung 195, 679–682 (2017). https://doi.org/10.1007/s00408-017-0033-2

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  • DOI: https://doi.org/10.1007/s00408-017-0033-2

Keywords

  • Alpha-1-antitrypsin deficiency
  • New SERPINA1 mutations
  • Bronchiectasis
  • Augmentation therapy