K Bork1, K Wulff2, G Witzke1, J Hardt3. 1. Department of Dermatology, Johannes Gutenberg University, Mainz, Germany. 2. University Medicine, Ernst Moritz Arndt University, Greifswald, Germany. 3. Department of Medical Psychology and Medical Sociology, Johannes Gutenberg University, Mainz, Germany.
Abstract
BACKGROUND: Hereditary angioedema with normal C1-INH may be linked to specific mutations in the coagulation factor 12 (FXII) gene (HAE-FXII) or mutations in genes that are still unknown (HAE-unknown). To assess the differences in transmission and inheritance, clinical features, and laboratory parameters between patients with HAE-FXII and HAE-unknown. METHODS: Sixty-nine patients with HAE-FXII from 23 unrelated families and 196 patients with HAE-unknown from 65 unrelated families were studied. RESULTS: Both HAE-FXII and HAE-unknown are inherited as autosomal-dominant traits with incomplete penetrance. The male to female ratio was 1 : 68 in HAE-FXII and 1 : 6.3 in HAE-unknown. The maternal to paternal transmission ratio was 35 : 14 for HAE-FXII and 109 : 12 for HAE-unknown. Mean age at onset of clinical symptoms was 20.3 years in patients with HAE-FXII and 29.6 years in patients with HAE-unknown. The incidence of asphyxiation due to angioedema was similar for HAE-FXII and HAE-unknown. Oral contraceptives and pregnancies had a significantly higher impact on HAE-FXII than on HAE-unknown. Slightly decreased C1-INH activity and C4 concentration were observed in more patients with HAE-FXII than HAE-unknown. Tests for FXI and FXII activity, plasminogen activator inhibitor 1, and activated partial thromboplastin time showed variability but no significant differences between the groups. No abnormalities were found for C1-INH protein, C1q, alpha2-macroglobulin, antithrombin III, and angiotensin-converting enzyme. In families with HAE-FXII, the number of female offspring with F12 mutations was significantly increased and that of male offspring was significantly decreased. CONCLUSIONS: HAE-FXII and HAE-unknown differ in various respects, including gender distribution, genetics, symptoms, and estrogen impact.
BACKGROUND:Hereditary angioedema with normal C1-INH may be linked to specific mutations in the coagulation factor 12 (FXII) gene (HAE-FXII) or mutations in genes that are still unknown (HAE-unknown). To assess the differences in transmission and inheritance, clinical features, and laboratory parameters between patients with HAE-FXII and HAE-unknown. METHODS: Sixty-nine patients with HAE-FXII from 23 unrelated families and 196 patients with HAE-unknown from 65 unrelated families were studied. RESULTS: Both HAE-FXII and HAE-unknown are inherited as autosomal-dominant traits with incomplete penetrance. The male to female ratio was 1 : 68 in HAE-FXII and 1 : 6.3 in HAE-unknown. The maternal to paternal transmission ratio was 35 : 14 for HAE-FXII and 109 : 12 for HAE-unknown. Mean age at onset of clinical symptoms was 20.3 years in patients with HAE-FXII and 29.6 years in patients with HAE-unknown. The incidence of asphyxiation due to angioedema was similar for HAE-FXII and HAE-unknown. Oral contraceptives and pregnancies had a significantly higher impact on HAE-FXII than on HAE-unknown. Slightly decreased C1-INH activity and C4 concentration were observed in more patients with HAE-FXII than HAE-unknown. Tests for FXI and FXII activity, plasminogen activator inhibitor 1, and activated partial thromboplastin time showed variability but no significant differences between the groups. No abnormalities were found for C1-INH protein, C1q, alpha2-macroglobulin, antithrombin III, and angiotensin-converting enzyme. In families with HAE-FXII, the number of female offspring with F12 mutations was significantly increased and that of male offspring was significantly decreased. CONCLUSIONS: HAE-FXII and HAE-unknown differ in various respects, including gender distribution, genetics, symptoms, and estrogen impact.
Keywords:
Angioedema; coagulation factor XII; hereditary angioedema type III; hereditary angioedema with normal C1 inhibitor; specific mutations in the F12 gene
Authors: Marcel Gutierrez; Camila L Veronez; Solange O Rodrigues Valle; Rozana Fátima Gonçalves; Mariana Paes Leme Ferriani; Adriana S Moreno; L Karla Arruda; Marcelo Vivolo Aun; Pedro Giavina-Bianchi; Maria Luiza Oliva Alonso; Joao B Pesquero; Anete S Grumach Journal: Clin Rev Allergy Immunol Date: 2021-03-23 Impact factor: 8.667
Authors: Pedro Giavina-Bianchi; Luisa Karla Arruda; Marcelo V Aun; Regis A Campos; Herberto J Chong-Neto; Rosemeire N Constantino-Silva; Fátima R Fernandes; Maria F Ferraro; Mariana P L Ferriani; Alfeu T França; Gustavo Fusaro; Juliana F B Garcia; Shirley Komninakis; Luana S M Maia; Eli Mansour; Adriana S Moreno; Antonio A Motta; João B Pesquero; Nathalia Portilho; Nelson A Rosário; Faradiba S Serpa; Dirceu Solé; Priscila Takejima; Eliana Toledo; Solange O.R Valle; Camila L Veronez; Anete S Grumach Journal: Clinics (Sao Paulo) Date: 2018-05-03 Impact factor: 2.365