title: Molecular mechanisms of alpha1-antitrypsin null alleles.
abstract: Alpha1-antitrypsin (alpha1-AT) is the most abundant circulating inhibitor of serine proteases and therefore is essential to normal protease-anti-protease homeostasis. Inheritance of two parental alpha1-AT deficiency alleles is associated with a substantially increased risk for development of emphysema and liver disease. In very rare circumstances individuals may inherit alpha1-AT null alleles. Null alpha1-AT alleles are characterized by the total absence of serum alpha1-AT. These alleles represent the extreme end in a continuum of alleles associated with alpha1-AT deficiency. The molecular mechanisms responsible for absence of serum alpha1-AT include splicing abnormalities, deletion of alpha1-AT coding exons and premature stop codons. While these alleles comprise only a small proportion of alpha1-AT alleles associated with profound alpha1-AT deficiency, studies of their molecular mechanisms provide valuable insights into the structure, gene expression and intracellular transport of alpha1-AT.
authors.affiliation: Department of Pediatrics, College of Medicine, Korea University, Seoul.
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Brantly
mesh_terms: D000483:Alleles; D018388:Codon, Terminator / Q000235:genetics; D004646:Emphysema / Q000235:genetics; D005091:Exons / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D008107:Liver Diseases / Q000235:genetics; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics*
chemical_list: D018388:Codon, Terminator