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

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

Author Veronez, Camila Lopes Autor UNIFESP Google Scholar
Silva, Elton Dias da Autor UNIFESP Google Scholar
Teixeira, Patricia Varela Lima Autor UNIFESP Google Scholar
Cagini, Nathalia Autor UNIFESP Google Scholar
Constantino-Silva, Rosemeire Navickas Google Scholar
Grumach, Anete Sevciovic Google Scholar
Mansour, Eli Google Scholar
Velloso, Licio A. Google Scholar
Pesquero, João Bosco Autor UNIFESP Google Scholar
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.
Keywords bradykinin
kinin B2 receptor
nitric oxide synthase
xmlui.dri2xhtml.METS-1.0.item-coverage Berlin
Language English
Date 2016
Published in Biological Chemistry. Berlin, v. 397, n. 4, p. 315-322, 2016.
ISSN 1431-6730 (Sherpa/Romeo, impact factor)
Publisher Walter De Gruyter Gmbh
Extent 315-322
Access rights Closed access
Type Article
Web of Science ID WOS:000374975000005

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