Novel Variants in Brugada Syndrome SCN1B to SCN4B Candidate Genes

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

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


Brugada syndrome is a cardiac channelopathy characterized by an increased risk of cardiac arrhythmias and sudden cardiac death. In 20% of Brugada syndrome patients mutations are found in the SCN5A gene. This gene codes for the alpha-subunit of the cardiac sodium channel. Other genes have also been associated with Brugada syndrome, mainly encoding cardiac ion channels or their auxiliary proteins. Among these genes are SCN1B and SCN3B, belonging to a family of 4 genes (SCN1B to SCN4B) encoding the sodium channel betasubunits that regulate sodium channel expression and gating properties.
One hundred Brugada syndrome probands, negative for SCN5A mutations, were analysed for variations in the beta-subunit genes (SCN1B, SCN2B, SCN3B and SCN4B) by Sanger sequencing. Seven potential causal variants were detected. Among these, two variants were chosen for further investigation.
A first variant was identified in SCN4B; a gene that has not yet been associated with Brugada syndrome. This variant is a nucleotide change upstream of the start codon in the minimal promoter region of the SCN4B gene. In silico comparison of this promoter region in different species reveals that the variant occurs at a highly conserved region. This might suggest an altered expression of SCN4B. A promoter-reporter clone was used to study the effect of this variant. The clone contains the SCN4B promoter region which controls the expression of a Gaussia luciferase reporter gene and an internal control to correct for transfection efficiency. Using site directed mutagenesis the variant was introduced in the promoter region of SCN4B. The promoterreporter clone with the wild type versus variant promoter was transfected in 293T cells. At first transfection conditions were optimized at the level of cell number, DNA concentration and harvest time. Preliminary results of two wild type and two mutant clones demonstrate a slight decrease in expression of the reporter gene in the variant promoter compared to the wild type promoter. Additional experiments are needed to check the reproducibility of the results to confirm the obtained data.
A second variant in the SCN1B beta-isoform is a two base pair deletion, which induces a frame shift resulting in an extended C-terminal region due to the abolishment of the stop codon. Another mutation in this isoform, resulting in a shortened amino acid sequence, has previously been described and associated with Brugada syndrome (Watanabe et al, jci,2008). cDNA-sequencing experiments are initiated to corroborate the presence of the SCN1B variant at the RNA-level.
Original languageEnglish
Title of host publicationAbstract book of the 13th Annual Meeting of the Belgian Society of Human Genetics
Number of pages1
Publication statusPublished - 15 Mar 2013

Publication series

Name13th Annual Meeting of the Belgian Society of Human Genetics


  • Brugada syndrome
  • SCN1B
  • SCN2B
  • SCN3B
  • SCN4B


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