Hereditary angioedema: clinical and genetic study of a Brazilian family

Abstract

Hereditary Angioedema (HAE) is a rare disease, potentially fatal, which is characterized by recurrent episodes of edema of the deep dermis, subcutaneous tissues and submucosa, affecting mainly the skin, gastrointestinal tract and larynx. The disease results from quantitative and/or functional deficiency of the C1 inhibitor (C1-INH, a regulatory protein of the Complement system), which occurs secondary to mutations of the coding gene for this protein (SERPING1). It is an autosomal dominant disease, with variable penetrance. Functional deficiency of C1-INH may remain silent for several decades, therefore the high fatality rate for airway obstruction (14% to 30%) justifies the importance and significance of improving knowledge of this syndrome. In the Allergy Clinics of the Clinical Hospital of the School of Medicine of Ribeirão Preto, we have identified a family with 126 related members, distributed in 5 generations, of whom 35 are possibly affected by HAE. In the literature, there are no reports of such a large number of individuals affected with HAE within one same family. Results of the complete sequence of the 8 exons of the SERPING1 gene in two patients of this family, carried out in a reference laboratory for diagnosis of HAE, revealed a heterozygotic deletion of one Citosine on exon 3, designated as c.351delC, which probably results in the deficiency of C1 inhibitor presented by these patients. In the present study, our objectives are to characterize clinically the patients of this family in detail, and to perform a genetic study of all members of the family, in order to determine whether the mutation detected in two of these individuals is responsible for the development and genetic transmission of Hereditary Angioedema. In addition, we will conduct functional studies to investigate whether there is transcription of the mutated gene in members of the family with Hereditary Angioedema. (AU)