Journal Article

Large Genomic Imbalances in Brugada Syndrome

Mates, Jesus, del Olmo, Bernat, Riuró, Helena, Porres, José Manuel, Sarquella-Brugada, Geòrgia, Picó, Ferran, Mademont-Soler, Irene, Pinsach-Abuin, Mel·lina, Pagans, Sara, Pérez-Serra, Alexandra, Selga, Elisabet, Iglesias, Anna, Arbelo, Elena, Cesar, Sergi, Coll, Mònica, Brugada, Ramon, Brugada, Josep, Campuzano, Óscar, Ferrer-Costa, Carles

2016

Overview

Brugada syndrome (BrS) is a form of cardiac arrhythmia which may lead to sudden cardiac death. The recommended genetic testing (direct sequencing of SCN5A) uncovers disease-causing SNVs and/or indels in ~20% of cases. Limited information exists about the frequency of copy number variants (CNVs) in SCN5A in BrS patients, and the role of CNVs in BrS-minor genes is a completely unexplored field. 220 BrS patients with negative genetic results were studied to detect CNVs in SCN5A. 63 cases were also screened for CNVs in BrS-minor genes. Studies were performed by Multiplex ligation-dependent probe amplification or Next-Generation Sequencing (NGS). The detection rate for CNVs in SCN5A was 0.45% (1/220). The detected imbalance consisted of a duplication from exon 15 to exon 28, and could potentially explain the BrS phenotype. No CNVs were found in BrS-minor genes. CNVs in current BrS-related genes are uncommon among BrS patients. However, as these rearrangements may underlie a portion of cases and they undergo unnoticed by traditional sequencing, an appealing alternative to conventional studies in these patients could be targeted NGS, including in a single experiment the study of SNVs, indels and CNVs in all the known BrS-related genes.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Arrhythmia / Arítmia / Genes / Genetic testing / Heart / Medical research / Mort sobtada / Sudden death