Although many genetic variants might be 'related' to the risk of a condition, whether they actually lead to disease is uncertain. According to the study authors, their approach might help to minimise the use of other clinical tests such as MRIs and echocardiograms, or the use of unnecessary medications.
Professor Joseph Wu, senior author said: 'Results from this study will help improve the interpretation and diagnostic accuracy of gene variants, especially in the era of personalized medicine and precision health.'
The research published in Circulation, initially analysed genetic information from 54 'healthy' or symptom-free volunteers with no history of heart disease. They looked specifically for 135 markers of hypertrophic cardiomyopathy and congenital heart disease, which are associated with sudden cardiac death.
A variant of the gene MYL3, often associated with hypertrophic cardiomyopathy, was detected in one participant as well as several family members. The mutation in this patient was heterozygous, meaning of the two genetic copies, one was mutated while the other was not. In heterozygous cells the non-mutated form of a gene can often compensate for the mutated variant.
The scientists collected the patient's blood cells and reprogrammed them into iPS (induced pluripotent stem) cells. These cells were edited using CRISPR/Cas9 technology to turn the heterozygous mutation into a homozygous one. These were then coaxed into becoming heart cells and with further analysis, the team predicted this patient's mutation to be benign and not a cause for heart disease in the future.
Dr Kiran Musunuru at the University of Pennsylvania in Philadelphia, who was not involved in this work, complimented the study but also highlighted its cost and time constraints. He told CNN: 'While it's very elegant, the major limitation of this work is that it took years of expensive work by a team of very talented scientists to do this for just one patient.'
Indeed Professor Wu estimated a six-month period and costs of US$10,000 to conduct this analysis on one genetic variation.
However, Professor Joseph Hill, of UT Southwestern Medical Centre in Dallas, Texas and editor of Circulation, stated the importance of this research. 'This study combined two new powerful technologies, induced pluripotent stem cells and CRISPR/Cas9 gene editing, to model a patient's heart in a dish and to test whether those heart cells manifested signs of disease,' he said.
'This approach heralds a new era of in vitro disease modelling and drug testing as pivotal elements of precision medicine.'