Researchers have carried out the first extensive analysis of genetic variants associated with Hypertrophic cardiomyopathy (HCM), the most common cause of sudden cardiac death. Their work will enable the development of new risk prediction tools to guide medical intervention.
HCM is a genetic disease of the heart muscle where the muscle wall of the heart becomes thickened. The hypertrophy (enlargement) is due to disorganised muscle fibres, most likely present from birth, that increase in severity over time.
BRC funding, as part of a push on health informatics, has enabled a team led by Professor Perry Elliott to set up a unique database of genetic and clinical information on patients and relatives with HCM. The team used high-throughput sequencing technology to study 223 unrelated patients and look at the genetic basis of HCM.
Previous research had suggested that approximately 50 per cent of people with HCM have mutations in genes that code for sarcomeric contractile proteins. However, an understanding of the relation between genetic abnormalities and disease severity remained elusive. This was partly because most studies examined small populations (often single families), were cross-sectional in design and frequently lacked data on disease expression in relatives.
Professor Elliott’s team have used next generation sequencing to show that sarcomere protein gene variants are present in up to 65 per cent of patients and that more than one causative mutation present in up to 10 per cent of individuals. Analysis of other genes implicated in inherited cardiac disease has identified a large number of rare variants that appear to modify expression of the disease.
These data will now be transferred into clinical practice by incorporating genetic data into new risk prediction tools that will guide medical intervention.
The study has been published in the Journal of Medical Genetics. To read the full text, please click here.
