Hereditary angioedema caused by the p.Thr309Lys mutation in the F12 gene: A multifactorial disease

摘要

Hereditary angioedema (HAE) related to estrogens, nowadays identified as HAE with normal Cl inhibitor (Cl-INH) function, is a kind of bradykinin (BK)-induced angioedema. In some cases, a mutation has been detected in the F12 gene (HAE-factor XII [HAE-FXII]).BK, the high-affinity ligand of type 2 BK receptor, is produced from high-molecular-weight kininogen upon cleavage by proteases (kallikrein, FXIIa, and plasmin), hereafter called kininoge-nases. BK is catabolized mainly by metallopeptidases (kininases): angiotensin-converting enzyme (ACE), aminopepti-dase P (APP), and carboxypeptidase N (CPN). BK level elevation produces an increase in endothelial permeability, vascular leakage, and angioedema.A schematic representation of BK generation and catabolism is shown in Fig preprinted with permission from Defendi et al6 [after modifications]).We report data from studies performed on a large 3-generation Spanish family with a strictly estrogen-precipitating angioedema phenotype in an attempt to investigate factors that might affect the clinical expression of this disease.