title: Genetic analysis of hereditary angioedema in a Brazilian family by targeted next generation sequencing.
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.
authors.forename: Camila Lopes
authors.initials: CL
authors.lastname: Veronez
authors.forename: Elton Dias
authors.initials: ED
authors.lastname: da Silva
authors.forename: Patrícia Varela
authors.initials: PV
authors.lastname: Lima Teixeira
authors.forename: Nathália
authors.initials: N
authors.lastname: Cagini
authors.forename: Rosemeire Navickas
authors.initials: RN
authors.lastname: Constantino-Silva
authors.forename: Anete Sevciovic
authors.initials: AS
authors.lastname: Grumach
authors.forename: Eli
authors.initials: E
authors.lastname: Mansour
authors.forename: Lício A
authors.initials: LA
authors.lastname: Velloso
authors.forename: João Bosco
authors.initials: JB
authors.lastname: Pesquero
mesh_terms: D000328:Adult; D054179:Angioedemas, Hereditary / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D001938:Brazil; D002648:Child; D005260:Female; D005820:Genetic Testing; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult