Missense Mutations in the Proline-Rich Region of Coagulation Factor XII in Hereditary and Idiopathic Angioedema.

Abstract Hereditary angioedema (HAE) is characterized by recurrent skin swelling, abdominal pain attacks, and potentially life-threatening upper airway obstruction. The two classic HAE types (I and II) are caused by mutations in the complement C1 inhibitor gene, resulting in a functional deficiency of C1 inhibitor. Recently, a novel type of hereditary angioedema has been described, these patients showing normal C1 inhibitor concentration and activity in plasma (HAE with normal C1 inhibitor, HAE type III). With few exceptions, all reported patients have been women, and exposition to estrogens appears to be an important precipitating factor. Screening of twenty unrelated female patients with …

Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor.

Hereditary angioedema is characterized by recurrent skin swelling, abdominal pain attacks, and potentially life-threatening upper airway obstruction. The two classic types are both caused by mutations within the complement C1 inhibitor gene. A recently described new type does not show a deficiency of C1 inhibitor and affects almost exclusively women. We screened twenty unrelated index patients with this new type of hereditary angioedema for mutations in the coagulation factor XII gene. Two different missense mutations were identified in exactly the same position within exon 9 of the F12 gene. 'Mutation 1' (1032C-->A), encountered in five patients, predicts a threonine-to-lysine substitution…

Missense mutations of coagulation factor XII in hereditary angioedema with normal complement C1 inhibitor

Hereditary angio-oedema with normal C1 inhibitor in a family with affected women and men

Recurrent angio-oedema is a sign of various acquired and inherited disease entities, including hereditary angio-oedema types I and II that result from a genetic deficiency of C1 inhibitor, and a recently described type of dominantly inherited angio-oedema, which does not show a deficiency of C1 inhibitor. Until now, this new type of hereditary angio-oedema, designated as hereditary angio-oedema type III, has been assumed to be a disorder specific to females. We now describe a four-generation family with dominantly inherited angio-oedema and normal C1 inhibitor in which, in contrast to all previous observations, not only five female but also three male family members were clinically affected…

Hereditary angioedema with normal C1 inhibitor: clinical symptoms and course.

Abstract Purpose A new type of hereditary angioedema was described recently. It was characterized by recurrent bouts of angioedema in various organs and normal C1 inhibitor and was observed mainly in women. Our aim was to conduct a detailed study of the clinical features of this condition. Methods A total of 138 patients with hereditary angioedema and normal C1 inhibitor who belonged to 43 unrelated families were examined through the use of standardized questionnaires. Results A majority of patients with hereditary angioedema and normal C1 inhibitor had skin swellings (92.8%), tongue swellings (53.6%), and abdominal pain attacks (50%). Laryngeal edema (25.4%) and uvular edema (21.7%) also w…

Hereditary angioedema type III, angioedema associated with angiotensin II receptor antagonists, and female sex

Recurrent episodes of skin angioedema and severe attacks of abdominal pain induced by oral contraceptives or hormone replacement therapy

Abstract Purpose Recurrent angioedema, characterized by skin swelling, colicky attacks of abdominal pain, and life-threatening laryngeal edema, can be either hereditary or acquired. According to anecdotal reports, it may be associated with use of oral contraceptives and hormone replacement therapy. We investigated potential interactions between these medications and various types of recurrent angioedema in a large cohort of women. Methods Women with recurrent angioedema (n = 516) underwent a thorough medical evaluation. They were then classified by type of angioedema, using standard criteria. Results Of the 516 women, 228 (44%) had used oral contraceptives or hormone replacement therapy, in…