Identification of Novel Variants in Brugada Syndrome SCN1B to SCN4B Candidate Genes

Uschi Peeters, Mary-Louise Bonduelle, Liszl Peirsman, Kristof Endels, Evrim Comurcu-Bayrak, Karine Breckpot, Pedro Brugada, Sonia Van Dooren

Research output: Chapter in Book/Report/Conference proceedingMeeting abstract (Book)Research

Abstract

Brugada syndrome (BrS) is characterized by an increased risk of cardiac arrhythmias and sudden cardiac death. 20% of BrS patients have mutations in the SCN5A gene, encoding the beta-subunit of the cardiac sodium channel. Other genes associated with BrS; are SCN1B and SCN3B. These belong to a family of 4 genes (SCN1B to SCN4B) encoding the beta-subunits that regulate SCN5A expression and gating properties.

Eighty three BrS probands, negative for SCN5A mutations, were analysed for variations in the beta-subunit genes by Sanger sequencing. Seven potential causal variants were detected. One variant was submitted to functional study.
The variant was identified in SCN4B upstream of the start codon in the minimal promoter region of the gene. In silico comparison of this promoter region in different species reveals that the variant occurs at a highly conserved region.
A promoter-reporter clone was used to study the effect of this variant. The promoter-reporter clone with the wild type or variant promoter was transfected in 293T cells. Initially transfection conditions were optimized. Expression experiments were performed in duplicate (n=2) and showed no statistically significant difference between the wild type and variant promoter. Therefore we do not consider this the cause of BrS in this patient.
Original languageEnglish
Title of host publicationVUB PhD Research Day 2013, Etterbeek, Belgium
Publication statusPublished - 2013

Keywords

  • Brugada Syndrome
  • beta subunits
  • SCN1-4B
  • promoter-reporter study

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