Genomic testing for Brugada syndrome – 8 genes minimal NGS panel

Cardiac arrhythmias constitute one of the main causes of morbidity and mortality. Congenital cardiac arrhythmias are a separate group of heart disorders resulting from defects in the electro-physiological properties of the heart. Specifically, coordination of cardiac activity includes, among other, the synchronous and sequential opening and closing of ion channels in response to the electrical potential and subsequent transmission of the action potential to each compartment of the heart.

Although environmental factors clearly contribute to arrhythmogenesis, family and population studies have also demonstrated an underlying genetic etiology. For example, mutations in >20 genes, which encode and/or modulate specific ion-channels, are associated with various forms of arrhythmias, occurring in an otherwise structurally normal heart.

As an example, Brugada Syndrome (BRS), is associated with mutations in at least seven different genes and is characterized by an increased risk of fatal ventricular arrhythmias. Sudden cardiac death (SCD), or sudden unexplained death, is a common cause of mortality, affecting all ages. The primary cause of sudden cardiac death in people older than 45 years is mainly due to atherosclerotic coronary artery disease. However, in individuals <45 years, genetic and hereditary defects in specific genes have been associated with the disease in up to 80% of cases.

We perform DNA sequence analysis, via Next Generation Sequencing (NGS) on a Genome Analyzer – Ion Proton platform, of all exons and intron-exon junctions/splice sites of the following 8 genes and Brugada syndrome types:

CACNA1C 114205 611875; 601005 Brugada syndrome 3 ; Timothy syndrome-Long QT AD
CACNB2 600003 611876 Brugada syndrome 4 AD
GPD1L 611778 611777 Brugada syndrome 2 AD
HCN4 605206 613123 Brugada syndrome 8 AD
KCNE3 604433 613119 Brugada syndrome 6 AD
SCN1B 600235 612838 Brugada syndrome 5 AD
SCN3B 608214 613120 Brugada syndrome 7 AD
SCN5A 600163 601144; 608567 Brugada syndrome 1; Sick sinus syndrome 1 AD, AR

Where possible and/or necessary, we carry out additional MLPA analysis in order to detect deletions/duplications of the genes (please consult the final test report).

The test is highly sensitive and complex, so it is necessary that the results are assessed by a specialized team of clinical and molecular geneticists, in order to ensure safe and reliable testing.

Proper clinical genetic assessment and genetic counseling, both before and after testing, is essential in order to determine the optimum testing strategy and also to communicate properly the concepts of pathological and normal.

InterGenetics is a Ion Torrent™ Certified Service Provider for Ion AmpliSeq sequencing on the Ion Proton platform.