Alpha1-Antitrypsin Deficiency and Emphysema Caused by Homozygous Inheritance of Non-Expressing Alpha1-Antitrypsin Genes

Abstract

EMPHYSEMA is a chronic disorder of the lower respiratory tract characterized by enlargement of the air space distal to the terminal bronchioles resulting from destruction of the alveolar walls.^{1 , 2} In the United States and Europe, approximately 2 percent of cases of emphysema are associated with a hereditary deficiency of α₁-antitrypsin,^{3 4 5 6} a 52-kd glycoprotein produced by hepatocytes and, to a lesser extent, mononuclear phagocytes.^{7 8 9 10 11 12 13 14 15 16 17} The single gene coding for α₁-antitrypsin is contained within a 10-kb segment of DNA composed of five exons on chromosome 14.18–20 The two parental alleles are codominantly expressed, and the α₁-antitrypsin . . .