PLoS ONE (Jan 2016)

Large Genomic Imbalances in Brugada Syndrome.

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

DOI
https://doi.org/10.1371/journal.pone.0163514
Journal volume & issue
Vol. 11, no. 9
p. e0163514

Abstract

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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.