Molecular defects in hereditary angioneurotic edema

Thirty-eight previously unreported, unrelated patients with hereditary angioneurotic edema were studied, and each was found to have a single mutation in the C1 inhibitor gene. On the basis of serine protease inhibitor crystal structure, these and published mutations affect critical domains in the reactive center loop, alpha-helices A, B, C, E, and F, and beta-sheets A and C. Almost all mutations, other than in the reactive center loop, occur at residues that are highly conserved among serine protease inhibitors, and the others are likely to interfere with molecular movement. These mutations begin to identify residues critical for molecular function of the C1 inhibitor molecule.