The Journal of Allergy and Clinical Immunology: In Practice
Original ArticleHereditary Angioedema with Normal C1 Inhibitor and F12 Mutations in 42 Brazilian Families
Section snippets
Subjects
After genetic testing, 102 Brazilian patients with recurrent episodes of subcutaneous edema without wheals, normal quantitative and/or functional C1-INH plasma levels, and no clinical response to high doses of antihistamines according to the criteria established by Cicardi et al1 were included in this study. All patients who showed mutations in the F12 gene known to be related to HAE were characterized as having FXII-HAE, a criterion for entering the study. Family history was a relevant factor
Genetic analyses
We performed genetic analyses of 195 individuals belonging to 42 unrelated families. One hundred two were symptomatic patients (86 females, 16 males) who presented pathogenic mutations in the F12 gene that were previously associated with HAE, and 32 were asymptomatic relatives (18 females, 14 males) who were carriers of F12 mutations. One hundred thirty-two patients (103 females, 29 males), distributed in 41 families, presented the pathogenic T328K mutation in the F12 gene (Figure 1). Two
HAE treatment
Management of patients with FXII-HAE focused on the discontinuation of potential trigger factors, including eOCs, HRT, or ACEI, and providing drug therapy, as recently reported by Bork et al.26 eOC was discontinued in 44 female patients who reported worsening of symptoms with these medications, and 27 switched to progestin as a contraceptive medication and/or were prescribed progestin as a treatment. In 1 patient who had symptoms that began after HRT was initiated, withdrawal of this medication
Discussion
In the present study, we described the clinical features of Brazilian patients with FXII-HAE from 42 families, who were evaluated at 9 HAE reference centers coordinated by the Brazilian Study Group on Hereditary Angioedema (GEBRAEH). Since the first report of this disease in Germany, several families presenting FXII-HAE have been identified in France, Spain, Italy, the United Kingdom, Luxemburg, Turkey, Australia, and Morocco,27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38 with T328K as the most
Acknowledgements
We thank Eduardo Costa, MD, PhD, from the Allergy and Immunology Division at the State University of Rio de Janeiro for providing blood samples from patients with HAE. We are grateful to Priscila Amorin Nicolicht from the Department of Biophysics at Universidade Federal de São Paulo (UNIFESP) and Mrs Marina Mendonça Dias from Ribeirão Preto Medical School, University of São Paulo, for technical assistance.
References (47)
- et al.
Hereditary angioedema with normal C1-inhibitor activity in women
Lancet
(2000) - et al.
Clinical, biochemical, and genetic characterization of a novel estrogen-dependent inherited form of angioedema
J Allergy Clin Immunol
(2000) - et al.
Hereditary angioedema caused by missense mutations in the factor XII gene: clinical features, trigger factors, and therapy
J Allergy Clin Immunol
(2009) - et al.
Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor
Biochem Biophys Res Commun
(2006) - et al.
Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III
Am J Hum Genet
(2006) - et al.
A novel mutation in the coagulation factor 12 gene in subjects with hereditary angioedema and normal C1 inhibitor
Clin Immunol
(2011) - et al.
Novel duplication in the F12 gene in a patient with recurrent angioedema
Clin Immunol
(2013) - et al.
Hereditary angioedema with normal C1 inhibitor: clinical symptoms and course
Am J Med
(2007) Hereditary angioedema with normal C1 inhibitor
Immunol Allergy Clin North Am
(2013)- et al.
Hereditary angioedema with F12 mutation: clinical features and enzyme polymorphisms in 9 Southwestern Spanish families
Ann Allergy Asthma Immunol
(2016)
A rare mutation in F12 gene in a patient with ACE inhibitor-induced angioedema
Ann Allergy Asthma Immunol
Clinical, biochemical, and genetic characterization of type III hereditary angioedema in 13 Northwest Spanish families
Ann Allergy Asthma Immunol
Hereditary angioedema with normal C1 inhibitor gene in a family with affected women and men is associated with the p.Thr328Lys mutation in the F12 gene
J Allergy Clin Immunol
First molecular confirmation of an Australian case of type III hereditary angioedema
Pathology
Genetic analysis of factor XII and bradykinin catabolic enzymes in a family with estrogen-dependent inherited angioedema
J Allergy Clin Immunol
Recurrent European missense mutation in the F12 gene in a British family with type III hereditary angioedema
J Dermatol Sci
Angioedema and estrogen-dependent angioedema with activation of the contact system
J Allergy Clin Immunol
Characterization of patients with angioedema without wheals: the importance of F12 gene screening
Clin Immunol
Differential regulation of kininogen gene expression by estrogen and progesterone in vivo
Biochim Biophys Acta
Estrogen induction and contact phase activation of human factor XII
Steroids
A common genetic polymorphism (46 C to T substitution) in the 5'-untranslated region of the coagulation factor XII gene is associated with low translation efficiency and decrease in plasma factor XII level
Blood
Mutation of angiopoietin-1 gene associates with a new type of hereditary angioedema
J Allergy Clin Immunol
Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group
Allergy
Cited by (48)
Hereditary angioedema with normal C1-inhibitor: Clinical and genetic characterization of 15 Portuguese unrelated families
2024, Annals of Allergy, Asthma and ImmunologyAngioedema With Normal Complement Studies: What Do We Know?
2023, Journal of Allergy and Clinical Immunology: In PracticeGenetic Variants Leading to Urticaria and Angioedema and Associated Biomarkers
2023, Journal of Allergy and Clinical Immunology: In PracticeGene Mutations Linked to Hereditary Angioedema in Solitary Angioedema Patients With Normal C1 Inhibitor
2023, Journal of Allergy and Clinical Immunology: In PracticePredicting quality parameters of wastewater treatment plants using artificial intelligence techniques
2023, Journal of Cleaner ProductionA patient with hereditary angioedema (HAE) with normal C1-INH and SLE with pregnancy
2023, Journal of Allergy and Clinical Immunology: Global
This work was supported by the São Paulo Research Foundation (FAPESP) (grant nos. 2011/24142-3, 2011/23439-2, 2013/02661-4, and 2014/27198-8). A.S.G. was supported by the Shire Research Program for Investigators.
Conflicts of interest: S. R. Valle is on the boards for Novartis, Sanofi, and CSL Behring and has received lecture fees from Novartis and Takeda. E. Mansour has received research and travel support from Shire; is on the CSL Behring board; and has received research support from Shire and CSL Behring. A. S. Grumach has received research support from São Paulo Research Foundation (FAPESP) (grant nos. 2011/24142-3, 2011/23439-2, 2013/02661-4, and 2014/27198-8) and Shire; has received travel support from Shire, CSL, Pharming, and Baxalta; is on the advisory boards for Shire, CSL, and LASID; has received consultancy fees from Shire, CSL, Pharming, Baxalta, and Viropharma; has received lecture fees from Shire, CSL, and Baxalta; and has received payment for developing educational presentations from Shire and CSL. The rest of the authors declare that they have no relevant conflicts of interest.
- ∗
These authors contributed equally to this work.