Supporting Families. Saving Lives.
Although DNA testing is becoming increasingly quick, cheap and easy to perform, the results are sometimes ambiguous: Gene mutations called “variants of uncertain significance” can create uncertainty about a patient’s risk for a disease.
“This is a really big problem,” said Joseph Wu, MD, PhD, professor of cardiovascular medicine and of radiology at the Stanford University School of Medicine. “If someone tells me I have a genetic variant that could cause sudden cardiac death, I’m going to be very scared. The result could be a lifetime of unnecessary worry for a patient when, in fact, the variant may be completely benign.”
Now, Wu and a team of researchers have developed a technique that could shed light on the significance of such variants. In a new paper, they discuss how they used advanced genetic-editing tools and stem cell technology to determine whether a 39-year-old patient with one of these mysterious mutations was at increased risk for a heart-rhythm condition called long QT syndrome, which can cause erratic heartbeats, fainting and sudden cardiac death.
“This is one of the first cases of using stem cells and genomics for precision cardiovascular medicine,” said Wu, who is also the Simon H. Stertzer, MD, Professor and director of Stanford’s Cardiovascular Institute.
The paper was published June 26 in the Journal of the American College of Cardiology. Wu is the senior author, and Stanford postdoctoral scholar Priyanka Garg, PhD, is the lead author.
The patient, who had a history of heart palpitations and lightheadedness, contacted a doctor worried about these symptoms. His family history showed he had a cousin who died of a heart attack playing soccer, a brother with a history of fainting and a grandfather who had four brothers die suddenly before the age of 40. A doctor ordered several electrocardiograms to test his heart function.
The results of those tests were cause for concern and, although ultimately inconclusive, his doctor chose to be cautious and prescribed the patient beta-blockers, a medication often used to treat mild cases of long QT syndrome. Genetic tests were inconclusive, as well, but showed the patient had a variant of uncertain significance on the KCNH2 gene. This was worrisome because several other mutations on this gene are known to cause long QT syndrome type 2, one of the most common types of the disorder.