HEREDITARY ANGIOEDEMA: IMPORTANCE OF MOLECULAR ANALYSIS IN DIAGNOSIS AND PATHOGENESIS AMONG BRAZILIAN FAMILIES

• Grant number: 11/23439-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): May 01, 2012
• Effective date (End): April 30, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Luisa Karla de Paula Arruda
• Grantee: Adriana Santos Moreno
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Angioedema is a clinical condition characterized by localized edema of the dermis and subcutaneous tissue, and it presents with episodes of swelling of the face, genitals or extremities, abdominal pain, and laryngeal edema which may lead to death by asphyxiation. Angioedema may be allergic; autoimmune; associated with infections; and secondary to the accumulation of bradykinin, including hereditary angioedema (HAE) due to mutations in the gene coding for C1 Inhibitor (SERPING1), familial angioedema associated with mutations of the Factor XII gene (F12), and acquired angioedema associated with autoimmune diseases, lymphoproliferative disorders and the use of Angiotensin-Converting Enzyme ACE inhibitors. HAE is an autosomal dominant disorder that results from deficiency of C1 Inhibitor (C1-INH) (types I and II) or gain of function mutations of Factor XII (type III). The mean time between onset of symptoms and diagnosis is 10 to 13 years, indicating that HAE is a disease that is not well known and under-diagnosed. The present study aims to study the pathogenesis and to characterize molecular abnormalities, describing the clinical, biological and genetic characteristics of patients in Ribeirão Preto, São Paulo and Rio de Janeiro with HAE. Patients will be evaluated clinically, and pedigrees of their families will be constructed. Blood samples will be collected for determination of C1-INH and C4, by nephelometry. Genomic DNA will be isolated from whole blood; PCR will be performed using specific primers and bi-directional sequencing of the eight exons of SERPING1 gene and of exon 9 of F12 will be carried out in symptomatic patients and asymptomatic family members. Molecular modeling studies will be developed, in paralel to functional correlations. This study will make it possible to create a Reference Center at FMRP to raise awareness and disseminate information on HAE to health professionals and to the general population in Brazil, aiming ultimately at improving diagnosis and treatment of patients with Hereditary Angioedema in our country.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VERONEZ, CAMILA LOPES; MORENO, ADRIANA S.; CONSTANTINO-SILVA, ROSEMEIRE NAVICKAS; MAIA, LUANA S. M.; FERRIANI, MARIANA P. L.; CASTRO, FABIO F. M.; VALLE, SOLANGE RODRIGUES; NAKAMURA, VICTOR KOJI; CAGINI, NATHALIA; GONCALVES, ROZANA FATIMA; et al. Hereditary Angioedema with Normal C1 Inhibitor and F12 Mutations in 42 Brazilian Families. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, v. 6, n. 4, p. 1209+, JUL-AUG 2018. (14/27198-8, 13/02661-4, 11/24142-3, 11/23439-2)