title: A novel SERPINA1 mutation causing serum alpha(1)-antitrypsin deficiency.
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.
authors.affiliation: Cancer Research Program, Garvan Institute of Medical Research, Sydney, Australia. d.saunders@garvan.org.au
authors.forename: Darren N
authors.initials: DN
authors.lastname: Saunders
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Tindall
authors.forename: Robert F
authors.initials: RF
authors.lastname: Shearer
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Roberson
authors.forename: Amy
authors.initials: A
authors.lastname: Decker
authors.forename: Jean Amos
authors.initials: JA
authors.lastname: Wilson
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Hayes
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D000515:alpha 1-Antitrypsin / Q000097:blood* / Q000737:chemistry / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood* / Q000235:genetics*
chemical_list: D050505:Mutant Proteins; C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin