According to Medical Xpress, Professor and Doctor Joseph Wu is looking into the complications of DNA testing and genetic mutations. Specifically, the confusion of gene mutations that are labeled “variants of uncertain significance.” To try and eradicate this grey and ambiguous area, Dr. Wu is using his new advanced genetic-editing tool to determine if an individual was at risk for long QT syndrome.
Long QT Syndrome Explained
Long QT Syndrome is a rare heart condition that can potentially potentially cause fast, chaotic heartbeats, which in turn cause sudden fainting spells or seizures. In some extreme cases, this heart beating can turn so erratic that the condition can cause sudden death. In those with long QT syndrome, the heart muscle takes longer than normal to recharge between beats, and this electrical disturbance is called a prolonged QT interval. Many of those who have long QT syndrome experience no signs or symptoms, but the most common symptoms of those that do occur are fainting and seizures. To learn more about the condition and some of the treatment options, click here.
The Issue
The problem with standard DNA testing is that it often gives patients ambiguous answers about certain gene mutations, claiming some to be “variants of uncertain significance,” which ultimately does not allow the patient to learn anything more about their risk.
“This is a really big problem,” said Dr. Joseph Wu. “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.”
Since this is such a challenging and frustrating type of diagnosis, Dr. Wu is setting out to find an alternative to this with his team. They recently developed a new technique that could help clear up the significance of these mysterious variants.
Specifically, in a paper they published, Wu and his team described their use of advanced genetic-editing tools in conjunction with stem cell technology to figure out if one individual was put at an increased risk for long QT syndrome. This was a major breakthrough for Wu and the team.
“This is one of the first cases of using stem cells and genomics for precision cardiovascular medicine,” said Wu.
More About the Patient
The individual who was tested had previously sought medical attention after noticing lightheadedness and heart palpitations. After the doctor ordered many electrocardiograms to test heart function, the results were finally inconclusive. That said, they were still concerning for the doctor, so the physician prescribed beta-blockers, which are frequently used to treat mild cases of long QT syndrome.
After this, the physician referred this individual to Dr. Wu, who wanted to figure out if the patient’s condition was pathogenic or benign.
The Discovery
Dr. Wu then set out to generate induced pluripotent stem cells, or cells that are capable of developing into just about any cell. These cells are taken from the patient’s blood and differentiated into heart cells that are actually capable of spontaneously beating in a culture dish. The convenient part about this extraction was that it contained the same exact genetic makeup of the patient, which included the patient’s “variant of uncertain significance” from previous testing, KCNH2.
“An advantage of generating patient-specific iPS heart cells is that you don’t have to use any invasive procedures on the patient to get them,” lead author Dr. Garg explained.
“You can generate a patient’s heart cells in a dish and study them just from a simple blood sample.”
After that, scientists utilized CRISPR, a well-known gene-editing tool, to fix the mutation in the patient’s gene. Tests in these heart cells then showed classic signs of long QT syndrome compared to cells from a healthy patient. To conclude, the results showed Wu and his fellow researchers that the patient indeed had a mild case of long QT syndrome.
In yet another study done by Dr. Wu and his team, the individual in testing received a better diagnosis from his uncertain significance conclusion. Dr. Wu’s testing technique revealed that a possible severe heart condition was actually benign in this patient and they were able to deliver him good and calming news.
“We were able tell the patient not to worry about it,” Wu said.
At the end of the day, this new technique will be incredibly useful in the future. Patients will be able to know more about their individual health and make more informed decisions about their treatment as a result.
“The results of these studies are particularly exciting to me because we used precision health methods to address an unmet need for a patient,” said Wu. “This means we now have the ability to go deeper and tell a patient what a variant of uncertain significance means.”
To read more about this exciting news, click here.
