Washington, May 11 : Brugada syndrome and/or cardiac conduction disease, characterised by sudden irregular heartbeats, has long been linked to mutations in the SCN5A gene, but scientists have now identified three mutations in another gene, called SCN1B, to be linked with this syndrome in those who lack SCN5A mutations.
People having Brugada syndrome and/or cardiac conduction disease are at an increased risk of sudden death due to irregular heartbeats (also known as cardiac arrhythmias).
And not all patients are detected with mutations in the SCN5A gene (which carries the information required for a cell to make the protein Nav1.5, the alpha-subunit of the main sodium channel in the heart).
So, Connie Bezzina and colleagues, at the University of Amsterdam, The Netherlands, have generated new data and have successfully identified mutations in SCN1B gene, which carries the information required for making two related sodium channel beta-subunits known as beta-1 and beta-1B.
During the study, the researchers found that expression of the intermediates that translate the genetic information into the beta-1 and beta-1B proteins was high in normal human heart tissue, particularly in the cells that conduct the electrical impulses that coordinate the beating of the heart.
This was found to support the hypothesis that mutant forms of these proteins might cause cardiac arrhythmias and/or defective conduction of the electrical impulses that regulate the heartbeat (the defects that lead to Brugada syndrome and cardiac conductance disease).
The observation that the mutant forms of beta-1 and beta-1B reduced Nav1.5 sodium currents in cell lines provided the functional evidence to support this hypothesis.
This led the authors to suggest that mutations in SCN1B can make individuals susceptible to Brugada syndrome and/or cardiac conductance disease.