Definitive Link of Mutation c.351delC and Development of Hereditary Angioedema in a Large Brazilian Family

Abstract

S U N D A Y 381 Definitive Link of Mutation c.351delC and Development of Hereditary Angioedema in a Large Brazilian Family M. F. Ferraro, A. S. Moreno, E. Castelli, A. P. Lange, E. A. Donadi, K. Bork, W. Sarti, L. K. Arruda; School of Medicine of Ribeirao Preto, Ribeirao Preto, BRAZIL, Johannes-Gutenberg University, Mainz, GERMANY. RATIONALE:We have previously described the identification of a novel SERPING1 mutation (c.351delC) in members of a large Brazilian family with Hereditary Angioedema (HAE). In the present study, we have aimed to verify the association of this mutation with the development of HAE in this family. METHODS: Family pedigree was constructed with 275 individuals distributed in 5 generations. Of those, 165 were interviewed, had blood samples collected and analyzed for DNA mutation and provided information about relatives. Sequencing of part of SERPING1 exon 3, including the c.351delC site, was carried out in those 165 individuals. Subjects referring history of recurrent episodes of angioedema and/or abdominal pain attacks underwent evaluation for HAE, which included measurements of C4 and C1 inhibitor (C1-INH). RESULTS: The c.351delC mutation is a single-nucleotide (cytosine) deletion on exon 3 of the SERPING1 gene. Twenty eight patients fulfilled diagnostic criteria for HAE and all of them presented the c.351delC mutation; five of these patients (ages 2, 6, 8, 26 and 53 years-old) were asymptomatic but had low levels of C1-INH and C4. Considerable variation in clinical presentation and severity of the disease was observed among these patients. The others 137 evaluated subjects do not have HAE or the c.351delC mutation. This family has the largest number of patients with HAE described so far, and the present study constitutes the first molecular analysis of HAE described in Latin America. CONCLUSIONS: We have provided definitive evidence to link a novel genetic mutation, c.351delC, to the development of HAE in patients of a Brazilian family