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

Autor:	Veronez CL; Center for Research and Molecular Diagnostic of Genetic Diseases, Department of Biophysics, Federal University of São Paulo, São Paulo, SP, Brazil., Moreno AS; Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil., Constantino-Silva RN; Division of Clinical Immunology, Faculdade de Medicina ABC, Santo André, SP, Brazil., Maia LSM; Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil., Ferriani MPL; Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil., Castro FFM; Division of Allergy and Clinical Immunology, School of Medicine of the University of São Paulo, São Paulo, SP, Brazil., Valle SR; Federal University of Rio de Janeiro, Cidade Universitária, Rio de Janeiro, RJ, Brazil., Nakamura VK; Center for Research and Molecular Diagnostic of Genetic Diseases, Department of Biophysics, Federal University of São Paulo, São Paulo, SP, Brazil., Cagini N; Center for Research and Molecular Diagnostic of Genetic Diseases, Department of Biophysics, Federal University of São Paulo, São Paulo, SP, Brazil., Gonçalves RF; Private Allergy and Immunology Clinic, Belo Horizonte, MG, Brazil., Mansour E; Division of Clinical Allergy and Immunology, School of Medicine, State University of Campinas, Campinas, SP, Brazil., Serpa FS; School of Medicine of Santa Casa de Misericordia of Vitoria, Vitoria, ES, Brazil., Coelho Dias GA; Division of Allergy and Immunology, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Piccirillo MA; Private Allergy and Immunology Clinic, Londrina, PR, Brazil., Toledo E; School of Medicine, State University of São José do Rio Preto, São José do Rio Preto, SP, Brazil., de Souza Bernardes M; Private Allergy and Immunology Clinic, Foz do Iguaçu, PR, Brazil., Cichon S; Division of Medical Genetics, University Hospital Basel, Basel, Switzerland; Department of Biomedicine, University of Basel, Basel, Switzerland; Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany., Stieber C; Institute of Human Genetics, University of Bonn School of Medicine & University Hospital of Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany; Center for Rare Diseases Bonn, University Hospital of Bonn, Bonn, Germany., Arruda LK; Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil., Pesquero JB; Center for Research and Molecular Diagnostic of Genetic Diseases, Department of Biophysics, Federal University of São Paulo, São Paulo, SP, Brazil., Grumach AS; Division of Clinical Immunology, Faculdade de Medicina ABC, Santo André, SP, Brazil. Electronic address: asgrumach@gmail.com.
Jazyk:	angličtina
Zdroj:	The journal of allergy and clinical immunology. In practice [J Allergy Clin Immunol Pract] 2018 Jul - Aug; Vol. 6 (4), pp. 1209-1216.e8. Date of Electronic Publication: 2017 Nov 08.
DOI:	10.1016/j.jaip.2017.09.025
Abstrakt:	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. (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu