Functional caracterization of the p.G184R, p.A297T, p.L251P, p.A457P and p.F477L variants found in the C1 esterase inhibitor gene - SERPING1

Abstract

Hereditary angioedema (HAE) is characterized by sudden episodes of swelling that cause pain, discomfort, and according to its location can cause disfigurement of the individual. Edema affects mainly the upper and lower extremities, gastrointestinal tract, genitalia and face. If not treated it can lead to death due to laryngeal edema HAE is an autosomal dominant disorder resulting from mutations in C1 esterase inhibitor (HAE types 1 and 2) or as a result of missense mutations in the Factor XII gene, leading to an overproduction of bradykinin (HAE type 3). The SERPING1 gene is responsible for HAE types 1 and 2, and several changes in this gene have been proven to be responsible for the phenotype displayed by the patients affected by this disease. Despite this knowledge, many changes still need to be studied and proved their connection with HAE. Thus, this study aims to analyze the expression and activity of C1 inhibitor containing some frequent mutations in our population (p.G184R, p.A297T, p.L251P, p.A457P and p.F477L) and for which there are no studies on the correlation with enzymatic activity. The results of this project should yield important information about the role of these mutations in the clinic of patients with HAE and guide genetic counseling and treatment. (AU)