Our studies have focused on determining the molecular basis of alpha1-antitrypsin (alpha1AT) deficiency variants utilizing natural mutations of the alpha1AT gene to assess structure-function relationships of alpha1AT and to explore regulatory mechanism of alpha1AT gene expression. In the past year the lab has identified an intronic sequence that enhances alpha1AT gene expression, characterized the molecular basis of the first splicing mutation in the alpha1AT gene, developed a model for understanding the molecular basis of heterogeneity among alpha1AT variants, begun the characterization of a group of frameshift mutations that terminate in the same structural region of the alpha1AT protein, determined the relationship of alpha1AT PI type to viral hepatitis. Furthermore the lab completed the kindred analysis and developed a screening assay for the novel null allele QOtrastervere. Finally, the alpha1AT phenotyping lab completed the initial identification of 1161 alpha1AT deficient individuals as part of the alpha1AT Deficiency Registry Study.
