A novel SERPINA1 mutation causing serum alpha(1)-antitrypsin deficiency

PLoS One. 2012;7(12):e51762. doi: 10.1371/journal.pone.0051762. Epub 2012 Dec 12.

Abstract

Mutations in the SERPINA1 gene can cause deficiency in the circulating serine protease inhibitor α(1)-Antitrypsin (α(1)AT). α(1)AT deficiency is the major contributor to pulmonary emphysema and liver disease in persons of European ancestry, with a prevalence of 1 in 2500 in the USA. We present the discovery and characterization of a novel SERPINA1 mutant from an asymptomatic Middle Eastern male with circulating α(1)AT deficiency. This 49 base pair deletion mutation (T379Δ), originally mistyped by IEF, causes a frame-shift replacement of the last sixteen α(1)AT residues and adds an extra twenty-four residues. Functional analysis showed that the mutant protein is not secreted and prone to intracellular aggregation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • HEK293 Cells
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutant Proteins / metabolism
  • Mutation / genetics*
  • alpha 1-Antitrypsin / blood*
  • alpha 1-Antitrypsin / chemistry
  • alpha 1-Antitrypsin / genetics*
  • alpha 1-Antitrypsin Deficiency / blood*
  • alpha 1-Antitrypsin Deficiency / genetics*

Substances

  • Mutant Proteins
  • SERPINA1 protein, human
  • alpha 1-Antitrypsin

Grant support

Supported by grants from the Cancer Institute New South Wales as a Career Development Fellowship (DNS and VMH) and a National Health and Medical Research Council of Australia training Fellowship (EAT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.