A mechanism for hereditary angioedema caused by a methionine-379 to lysine substitution in kininogens

Hereditary angioedema (HAE) is associated with episodic kinin-induced swelling of skin and mucosal membranes. Most HAE patients have low plasma C1-inhibitor activity, leading to increased generation of the protease plasma kallikrein (PKa) and excessive release of the nanopeptide bradykinin from high-molecular-weight kininogen (HK). However, disease causing mutations in at least 10% of HAE patients appear to involve genes for proteins other than C1-inhibitor. A point mutation in the Kng1 …