Genomic testing for cardiac arrhythmias – 40 genes 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.

Generally, the majority of heart diseases associated with arrhythmias are expressed and inherited in an autosomal dominant manner, which means that individuals with a mutation in only one of the two copies of a gene have a particularly high risk of manifesting the disease and all first-degree relatives of a patient have a 50% risk of inheriting the disease. It is also important to bear in mind that different mutations in the same gene can lead to the expression of different types of a cardiogenetic disease.

Previous genetic testing options for cardiogenetic disorders and arrhythmias were extremely slow (months or years) and incomplete (testing ofl only a few genes) and as a result the underlying genetic causes-gene mutations were not revealed in patients and relatives with hereditary heart diseases.

To the extent, therefore, that until now genetic testing was selective, incomplete and often expensive, parallel analysis of all known genes through genomic testing affords successful and final diagnosis in a single step.

The identification of the pathogenic mutation is important for genetic counseling of patients and families, for facilitating timely diagnosis in individuals at risk. Moreover, in many cases the exact knowledge of the genetic cause may lead to a more effective management of the symptoms and to determine the appropriate individualized medication or treatment.

Recently, the introduction of Next Generation Sequencing (NGS) technology has become a highly effective diagnostic strategy, through the parallel analysis of a large number of genes associated with all known types of hereditary arrhythmias.

InterGenetics has developed and offers an NGS panel for the genomic analysis of all 40 genes, associated with a wide spectrum of cardiac arrhythmias, irrespective of the mode of inheritance.

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 40 genes, allowing us to detect >98% of all pathogenic mutations of the genes through the use of specially developed bioinformatics tools, thus providing in a single step an increased clinical sensitivity and performance compared to single gene testing.

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.

See also genomic testing for Short & Long QT syndromes 12 genes NGS minimal panel and genomic testing for Brugada syndrome 8 genes NGS minimal panel.

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