A rapid, simple blood test has been developed that accurately can detect all known genes associated with inherited heart conditions which are characterized by marked genetic and allelic heterogeneity and require extensive sequencing for genetic characterization.

Inherited heart conditions are caused by gene mutations that have been passed down from relatives. If a mother possesses one of these faulty genes, there is a 50% chance that they will pass the mutation on to their child. These heart conditions include aortic valve disease, structural heart disease, long and short QT syndrome, Noonan syndrome, familial atrial fibrillation and most cardiomyopathies.

Scientists at the Imperial College London (UK) working with their colleagues analyzed the blood samples of 348 participants from the National Heart Center (Singapore). Genomic DNA was extracted from blood using Prepito DNA Blood 600 kit (Perkin Elmer, Waltham, MA, USA) for targeted sequencing; EZ1 DSP DNA blood 48 kit (Qiagen, Venlo, Netherlands) for whole exome sequencing, (WES) or the Qiagen QIAsymphony DNA kit for whole genome sequencing (WGS).

Quality and quantity of extracted DNA were assessed by an ultraviolet-visible spectrophotometer. For targeted sequencing pooled libraries were prepared using the inherited cardiac conditions (ICC) panel and were sequenced on the MiSeq (108 samples) or NextSeq 500 (144samples) benchtop sequencers (Illumina; San Diego, CA, USA) using paired-end, 150 bp reads. Pathogenic or likely pathogenic variants of 26 samples were identified using the ICC panel in a study cohort of 35 samples was subjected to Sanger sequencing.

The new test used next-generation sequencing to simultaneously identify 174 genes known to increase the risk of 17 inherited heart conditions. The team found that the test was able to quickly identify all gene mutations in the blood samples that were associated with the 17 inherited heart conditions with up to 100% accuracy. The assay has better performance, shorter turnaround times, lesser informatics requirements and lower sequencing costs as compared to the WES, deep WES, and WGS. The assay is called the TruSight Cardio Sequencing Kit.

James S. Ware, MD, PhD, a cardiologist and coauthor of the study said, “Without a genetic test, we often have to keep the whole family under regular surveillance for many years, because some of these conditions may not develop until later in life. This is hugely costly for both the families and the health system. By contrast, when a genetic test reveals the precise genetic abnormality causing the condition in one member of the family, it becomes simple to test other family members. Those who do not carry the faulty gene copy can be reassured and spared countless hospital visits. This new comprehensive test is increasing the number of families who benefit from genetic testing.” The study was published on February 17, 2016, in the Journal of Cardiovascular Translational Research.

Related Links:
Imperial College London 
Singapore National Heart Center
Illumina