In most people, heart disease develops through a lifetime of cigarettes, trans fats or high glycemic foods. For only a minority of patients does the cause lie in their genes. But when such atypical patients show up for treatment, figuring out why their hearts aren’t working has been a huge challenge for their doctors. The process of deciding if a heart patient’s problem is genetic and, if so, which gene defects might be causing the problem can take weeks or months, cost a thousand dollars or more, and, at the end, leave physicians still scratching their heads over a mountain of uncertain data.
A new genetic test being developed by pathologist Kitchener Wilson, MD, PhD and cardiology and radiology professor Joseph Wu, MD, PhD, may be able to accurately pinpoint the likely genetic causes of a heart patient’s elusive condition in just a couple of days.
Wilson and Wu say that for a patient with a heart condition that’s difficult to diagnose, it makes no sense to sequence the entire 22,000-gene human genome. Such whole-genome sequencing is costly, time consuming, and produces data marred by small but important errors.
So, taking a more focused approach, 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. Materials for the new assay cost about $100, and results are back within three days.
Their approach — surveying a small subgroup of relevant genes instead of the whole genome — is already used to look for other genetic diseases, such as cystic fibrosis. But cystic fibrosis results from mutations in a single gene. “The heart diseases are more challenging just because there are so many genes to sequence,” says Wilson.
Wilson and Wu’s assay is a variation on “complementary long padlock probes,” or cLPPs, a class of genetic probes developed at the Stanford Genome Technology Center. These simple probes accurately target specific parts of the genome and are easily customized to target genes of interest. Wilson and Wu spearheaded the effort to put cLPPs to work on genes connected with heart problems and reported their work in the journal Circulation Research, with Wu as senior author and Wilson as first author.
If further tests validate the assay, it could shorten the time it takes to diagnose difficult or unusual heart disease cases—like that of basketball player Hank Gathers above — hastening appropriate treatment for atypical cardiac patients.
Previously: At Stanford Cardiovascular Institute’s annual retreat, a glimpse into the future of cardiovascular medicine and Coming soon: A genome test that costs less than a new pair of shoes
Photo by: Liviu Ghemaru