A new genetic test has been developed by researchers at the Stanford University School of Medicine for those heart patients whose illness is not caused due to cigarette smoking, trans fats or high glycemic foods. This test may be able to accurately pinpoint the likely genetic causes of their conditions in just a couple of days.
Kitchener Wilson instructor of pathology and Joseph Wu professor of cardiovascular medicine and of radiology, teamed up with a group of genome-sequencing specialists to develop the new technique. This technique is a better way to test cardiac patients for any genes that might be causing their problems.
"The standard genome sequencing involves thousands of genes which costs $1,000 or more and can take weeks or months to get results. For a patient with a heart condition that's difficult to diagnose, it makes no sense to sequence the entire 22,000-gene genome, since fewer than 200 genes are known to affect the heart," said Wilson and Wu. Also whole-genome sequencing typically contains mistakes, so key mutations might be missed.
Wilson and Wu's team designed a streamlined assay or test that looks at just the 88 genes known to carry mutations that cause heart problems. The results are back within 3 days and the new test costs about $100. Wilson and Wu are first and senior authors, respectively, on a paper describing the assay that will be published online in Circulation Research
The approach which involves surveying a small group of relevant genes instead of the whole genome, is already used to test for other diseases such as cystic fibrosis. But cystic fibrosis involves only one gene with hundreds of variants. "By comparison, the heart diseases are more challenging just because there are so many genes to sequence," said Wilson. "To do that accurately has been difficult and, until now, too expensive for most labs."
Simple genetic probes testing is not for the typical, older cardiac patient who comes in with chest pain, the result of a lifetime of poor diet and little exercise. "Those patients can be treated with standard treatments, such as surgical interventions. But what if a 30-year-old woman comes in with chest pain and her doctors can't find any obvious reason why she should be having heart problems at such a young age?" said Wu, who is also the director of Stanford's Cardiovascular Institute. That could be the moment for doctors to break out the complementary long padlock probes for inherited heart disease.
cLPPs or Complementary long padlock probes were developed at the Stanford Genome Technology Center. These simple probes target specific parts of the genome and can be made in large batches at low cost. They are easily customized to target different genes because of their simplicity. Wilson and Wu spearheaded the effort to put cLPPs to work diagnosing cardiac diseases.
The cLPP approach was validated with preliminary test of the assay on blood samples and some skin samples from 29 participants from families with inherited heart disease, said researchers. The heart disease cLPP assay was cheaper, faster and more accurate than whole-genome assays.
The Stanford teams plans to test the technique on a group of 200-300 patients. On the other hands Wilson and Wu are offering the test free to any research lab that wants to try it. "They can just email me and we'll send them the assay, and then they can do it in their own lab—as long as they have some experience with next-generation sequencing," said Wilson.
The assay will help in shortening the time it takes to diagnose difficult or unusual heart disease cases, said Wu. "Suppose you have a 60-year-old patient who comes in with heart failure," he said. "We do the angiogram and we find he has no history of heart attack or other issues, and yet the heart is not performing well. We also find that several of his family members have similar heart conditions. So if we run the new genetic test and find the man's illness has a genetic cause, such as dilated cardiomyopathy, we now have both a cause and a diagnosis, and we can initiate treatment right away."
"Not having that result delays diagnosis and increases costs because you're going through a whole bunch of tests—sometimes it becomes a fishing expedition, which can be frustrating to both the physician and the patient," Wu added. "But perhaps the most important benefit is that you can give the patient accurate answers about his or her disease."
Wilson and Wu said the genome technology group has been working on the cLPP technique for a long time. "Our goal is to make genetic testing more accessible to more people," Wilson said. "We want to democratize it. For now, we're going to release it free of charge: Researchers can get samples of the assay so they can run it themselves. We're also releasing all of the technical data for the probes so researchers can recreate and modify the probes themselves. In some ways it's making genetic testing open source."
The development of the new test is an example of Stanford Medicine's focus on precision health, which aims to enable researchers and physicians to better predict individual risks for specific diseases, develop approaches to early detection and prevention, and help clinicians make real-time decisions about the best way to care for patients.