Publications

Abstract

Mutations in the SERPINA1 gene can cause deficiency in the circulating serine protease inhibitor alpha(1)-Antitrypsin (alpha(1)AT). alpha(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 alpha(1)AT deficiency. This 49 base pair deletion mutation (T379Delta), originally mistyped by IEF, causes a frame-shift replacement of the last sixteen alpha(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.