A Novel SERPINA1 Mutation Causing Serum Alpha1-Antitrypsin Deficiency |
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| Authors: | Darren N. Saunders Elizabeth A. Tindall Robert F. Shearer Jacquelyn Roberson Amy Decker Jean Amos Wilson Vanessa M. Hayes |
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| Affiliation: | 1. Cancer Research Program, Garvan Institute of Medical Research, Sydney, Australia.; 2. Kinghorn Cancer Centre, Sydney, Australia.; 3. St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia.; 4. Medical Genetics, Henry Ford Hospital, Detroit, Michigan, United States of America.; 5. Quest Diagnostics Nichols Institute, Valencia, California, United States of America.; University of Giessen Lung Center, Germany, |
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| Abstract: | Mutations in the SERPINA1 gene can cause deficiency in the circulating serine protease inhibitor α1-Antitrypsin (α1AT). α1AT 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 α1AT deficiency. This 49 base pair deletion mutation (T379Δ), originally mistyped by IEF, causes a frame-shift replacement of the last sixteen α1AT residues and adds an extra twenty-four residues. Functional analysis showed that the mutant protein is not secreted and prone to intracellular aggregation. |
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