Whole exome sequencing of patients with hereditary angioedema of unknown etiology

• Grant number: 16/23364-6
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: April 01, 2017
• End date: March 31, 2018
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: João Bosco Pesquero
• Grantee: Renan Paulo Martin
• Supervisor: Nara Lygia de Macena Sobreira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: Johns Hopkins University (JHU), United States
• Associated to the scholarship: 14/20965-3 - In silico study of genetic mutations causing hereditary angioedema, BP.PD

Abstract

The hereditary angioedema (HAE) is an autosomal dominant inherited disease characterized by painful edema episodes with variable localization and severity. Most of diagnosed patients present either mutation on C1 inhibtor gene (C1-INH), with abnormal levels or functionality (HAE type I and II, respectively) or Factor 12 (FXII) gene (HAE Type 3). These mutations leads to a super production of bradykinin (BK), the peptide responsible for edema formation. In addition, there is a HAE of unknown molecular etiology, where the patients present the same symptoms but no mutation in both known genes. In order to discover possible candidate genes involved in the pathophysiology of HAE of unknown molecular basis, we propose to use next generation sequencing (NGS) to investigate individuals with HAE and no mutation in SERPING1 or F12. Additionally, we intend to look for modifiers of HAE disease in families with the same causative mutation and variable clinical manifestations. The sequencing will be carried out with Ion Proton at Prof Joao Bosco Pesquero Laboratory and the acquired data will be analyzed with PhenoDB software at Dr. Nara Sobreira's laboratory at Johns Hopkins University. The results of the present project could improve the knowledge on HAE disease field and help to improve the diagnoses and life quality of the patients.