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

Publication date: Available online 8 November 2017
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Camila Lopes Veronez, Adriana S. Moreno, Rosemeire Navickas Constantino-Silva, Luana S.M. Maia, Mariana P.L. Ferriani, Fábio F.M. Castro, Solange Rodrigues Valle, Victor Koji Nakamura, Nathália Cagini, Rozana Fátima Gonçalves, Eli Mansour, Faradiba Sarquis Serpa, Gabriela Andrade Coelho Dias, Miguel Alberto Piccirillo, Eliana Toledo, Marli de Souza Bernardes, Sven Cichon, Christiane Stieber, L. Karla Arruda, João Bosco Pesquero, Anete Sevciovic Grumach
BackgroundHereditary 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.ObjectivesOur 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.MethodsWe evaluated a group of 195 individuals, which included 102 patients clinically diagnosed with FXII-HAE and their 93 asymptomatic relatives.ResultsGenetic 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.ConclusionsOur 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.