Hereditary Angioedema with Normal C1 Inhibitor and F12 Mutations in 42 Brazilian Families

Author(s):Show less -

Veronez, Camila Lopes ^[1] ; Moreno, Adriana S. ^[2] ; Constantino-Silva, Rosemeire Navickas ^[3] ; Maia, Luana S. M. ^[2] ; Ferriani, Mariana P. L. ^[2] ; Castro, Fabio F. M. ^[4] ; Valle, Solange Rodrigues ^[5] ; Nakamura, Victor Koji ^[1] ; Cagini, Nathalia ^[1] ; Goncalves, Rozana Fatima ^[6] ; Mansour, Eli ^[7] ; Serpa, Faradiba Sarquis ^[8] ; Coelho Dias, Gabriela Andrade ^[9] ; Piccirillo, Miguel Alberto ^[10] ; Toledo, Eliana ^[11] ; Bernardes, Marli de Souza ^[12] ; Cichon, Sven ^{[13, 14, 15]} ; Stieber, Christiane ^{[16, 17, 18, 19]} ; Arruda, L. Karla ^[2] ; Pesquero, Joao Bosco ^[1] ; Grumach, Anete Sevciovic ^[3]

Affiliation:Show less -

^[1] Univ Fed Sao Paulo, Dept Biophys, Ctr Res & Mol Diagnost Genet Dis, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med, Ribeirao Preto, SP - Brazil

^[3] Fac Med ABC, Div Clin Immunol, Santo Andre, SP - Brazil

^[4] Univ Sao Paulo, Sch Med, Div Allergy & Clin Immunol, Sao Paulo, SP - Brazil

^[5] Fed Univ Rio Janeiro, Cidade Univ, Rio De Janeiro, RJ - Brazil

^[6] Private Allergy & Immunol Clin, Belo Horizonte, MG - Brazil

^[7] Univ Estadual Campinas, Sch Med, Div Clin Allergy & Immunol, Campinas, SP - Brazil

^[8] Santa Casa de Misericordia Vitoria, Sch Med, Vitoria, ES - Brazil

^[9] Univ Estado Rio De Janeiro, Div Allergy & Immunol, Rio De Janeiro, RJ - Brazil

^[10] Private Allergy & Immunol Clin, Londrina, PR - Brazil

^[11] State Univ Sao Jose do Rio Preto, Sch Med, Sao Jose Do Rio Preto, SP - Brazil

^[12] Private Allergy & Immunol Clin, Foz Do Iguacu, PR - Brazil

^[13] Univ Hosp Basel, Div Med Genet, Basel - Switzerland

^[14] Univ Basel, Dept Biomed, Basel - Switzerland

^[15] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich - Germany

^[16] Univ Bonn, Sch Med, Inst Human Genet, Bonn - Germany

^[17] Univ Hosp Bonn, Bonn - Germany

^[18] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn - Germany

^[19] Univ Hosp Bonn, Ctr Rare Dis Bonn, Bonn - Germany

• Document type: Journal article
• Source: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE; v. 6, n. 4, p. 1209+, JUL-AUG 2018.
• Web of Science Citations: 10

Abstract

BACKGROUND: Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) is a rare condition with clinical features similar to those of HAE with C1-INH deficiency. Mutations in the F12 gene have been identified in subsets of patients with HAE with normal C1-INH, mostly within families of European descent. OBJECTIVES: Our aim was to describe clinical characteristics observed in Brazilians from 42 families with HAE and F12 gene mutations (FXII-HAE), and to compare these findings with those from other populations. METHODS: We evaluated a group of 195 individuals, which included 102 patients clinically diagnosed with FXII-HAE and their 93 asymptomatic relatives. RESULTS: Genetic analysis revealed that of the 195 subjects, 134 individuals (77.6% females) carried a pathogenic mutation in F12. The T328K substitution was found in 132 individuals, and the c.971\_1018 + 24del72 deletion was found in 2 patients. The mean age at onset of symptoms in patients with FXII-HAE was 21.1 years. The most common symptoms were subcutaneous edema (85.8% of patients), abdominal pain attacks (69.7%), and upper airway edema (32.3%). Of male individuals carrying F12 mutations, 53.3% (16 of 30) were symptomatic. Compared with reports from Europe, fewer female patients (68.6%) reported an influence of estrogen on symptoms. CONCLUSIONS: Our study included a large number of patients with FXII-HAE, and, as the first such study conducted in a South American population, it highlighted significant differences between this and other study populations. The high number of symptomatic males and patients with estrogen-independent FXII-HAE found here suggests that male sex and the absence of a hormonal influence should not discourage clinicians from searching for F12 mutations in cases of HAE with normal C1-INH. (C) 2017 American Academy of Allergy, Asthma \& Immunology. (AU)

• FAPESP's process: 14/27198-8 - Establishment of a center of genetic and molecular research for clinical challenges
• Grantee: João Bosco Pesquero
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/02661-4 - Genetics of hereditary angioedema
• Grantee: João Bosco Pesquero
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/24142-3 - Plasma Kallikrein Role in Hereditary Angioedema: Genetics and Functional Analysis.
• Grantee: Camila Lopes Veronez
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/23439-2 - HEREDITARY ANGIOEDEMA: IMPORTANCE OF MOLECULAR ANALYSIS IN DIAGNOSIS AND PATHOGENESIS AMONG BRAZILIAN FAMILIES
• Grantee: Adriana Santos Moreno
• Support Opportunities: Scholarships in Brazil - Post-Doctoral