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Licensed Unlicensed Requires Authentication Published by De Gruyter January 8, 2016

Genetic analysis of hereditary angioedema in a Brazilian family by targeted next generation sequencing

  • Camila Lopes Veronez , Elton Dias da Silva , Patrícia Varela Lima Teixeira , Nathália Cagini , Rosemeire Navickas Constantino-Silva , Anete Sevciovic Grumach , Eli Mansour , Lício A. Velloso and João Bosco Pesquero EMAIL logo
From the journal Biological Chemistry

Abstract

Hereditary angioedema (HAE) is accompanied by an overproduction of bradykinin (BK) as the primary mediator of swelling. Although many proteins may be involved in regulating the wide spectrum of HAE symptoms, most studies have only focused on C1-INH and FXII. For the first time, a next generation sequencing (NGS) method was applied to develop a robust, time- and cost-effective diagnostic and research tool to analyze selected genes related to HAE. The entire coding region and the exon-intron boundaries of 15 genes from 23 subjects of a Brazilian family, nine of whom were symptomatic, were analyzed by NGS. One new mutation found uniquely in the nine symptomatic patients, p.Ala457Pro in the SERPING1 gene, was estimated as likely to be pathogenic (PolyPhen-2 software analysis) and is the main candidate to be responsible for HAE in these patients. Alterations identified in a few asymptomatic individuals but also found in almost all symptomatic patients, such as p.Ile197Met (HMWK), p.Glu298Asp (NOS3) and p.Gly354Glu (B2R), may also be involved in modulating patient-specific symptoms. This NGS gene panel has proven to be a valuable tool for a quick and accurate molecular diagnosis of HAE and efficient to indicate modulators of HAE symptoms.


Corresponding author: João Bosco Pesquero, Department of Biophysics, Federal University of São Paulo (UNIFESP), Rua Pedro de Toledo 669, 9° andar, São Paulo, 04039-032, Brazil, e-mail:

Acknowledgments

We thank Prof. Dr. Michael Bader and Prof. Dr. Russel Hodge for helpful conversation and a critical reading of the original manuscript, and Dr. Renan Paulo Martin for the help in the final drafts. This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant/Award Number: ‘2013/02661-4 and 2011/24142-3’). LAV belongs to Obesity and Comorbidities Research Center, supported by grants from FAPESP.

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Received: 2015-7-22
Accepted: 2015-12-24
Published Online: 2016-1-8
Published in Print: 2016-4-1

©2016 by De Gruyter

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