Saunders DN, Tindall EA, Shearer RF, Roberson J, Decker A, Wilson JA, Hayes VM
A Novel SERPINA1 Mutation Causing Serum Alpha(1)-Antitrypsin Deficiency.
PloS one. 2012 Dec 01; 7: e51762.
Mutations in the SERPINA1 gene can cause deficiency in the circulating serine protease inhibitor ?(1)-Antitrypsin (?(1)AT). ?(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 ?(1)AT deficiency. This 49 base pair deletion mutation (T379?), originally mistyped by IEF, causes a frame-shift replacement of the last sixteen ?(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.