03 February 2023
Mutations raise risk of dangerous heart condition
Published online 24 July 2013
Brugada syndrome is a rare genetic disorder in which the heart's normal rhythm is disrupted, increasing the risk of sudden cardiac death. Twenty percent of cases are associated with mutations of SCN5A, a gene which provides instructions for formation of sodium channels.
An international team of researchers led by Connie Bezzina from the Academic Medical Center in the Netherlands and Richard Redon from the Institut du Thorax in France, and including Peter Schwartz from King Saud University in Riyadh, performed a genome-wide association study which included 312 individuals with Brugada syndrome and 1,115 controls, publishing their findings this week in Nature Genetics１.
The researchers discovered that susceptibility to Brugada syndrome, previously thought to be linked to only one gene mutation, increases with other risk alleles found at the SCN10A and SCN5A genes, which are both involved in cardiac conduction. This indicates that genetic variations affecting electrical conduction in the heart may make patients more susceptible to heart rhythm disorders.
The team also identified a risk allele near the HEY2 gene which regulates electrical activity of the heart. This shows that Brugada syndrome may originate during heart development due to altered regulation of transcription during gene expression. People with all risk alleles had an unexpectedly high susceptibility to the disease.
- Bezzina, C.R et al. Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death. Nature Genetics (2013) doi:10.1038/ng.2712