Photo of woman and man with their two young daughters, posed in front of trees.

Photo courtesy Amy Hower: Amy Hower with her husband and children. Hower turned to Stanford Health Care to find out the genetic cause of her heart condition. “The results I got were life-changing for me,” she said.

Stanford Medicine News Center - February 11th, 2021 - by Hanae Armitage

A new Stanford Medicine service analyzes patients’ entire genetic code for information that could reveal the roots of diseases.

The service is based on whole genome sequencing, a test that maps all of an individual’s DNA.

Genes, which are blocks of DNA that help determine a person’s traits, can contain mutations that lead to disease. Genome sequencing can help scientists and doctors identify the genes behind a particular illness. The test can provide valuable insights, such as someone’s risk of developing a specific disease or whether a disease runs in a family, and help physicians tailor effective treatments, said Euan Ashley, MB ChB, DPhil, professor of medicine, of genetics and of biomedical data science at Stanford.

Known as the Cardiovascular Genome Panel, the genome sequencing service at Stanford Medicine launched Jan. 25. It’s now available to patients diagnosed with inherited cardiovascular disease. Ashley, who heads the service, plans to expand it into other specialties, such as cancer care.

“This is a really progressive type of testing,” said Stuart Scott, PhD, director of the Clinical Genomics Laboratory, which provides the service. “To our knowledge, we are the first to offer clinical, whole-genome, sequencing-based, diagnostic panel testing. I think over the next few years we’ll see a big push in other hospitals and academic medical centers to do this as well.”

The goal of integrating genome sequencing into patient care is to enhance diagnostic power. A doctor with the entire genome sequence at his or her disposal is more likely not only to make the correct diagnosis, but also find the cause of the disease.

A vision realized

Ashley has envisioned in-house genome sequencing since he and Steve Quake, PhD, professor of bioengineering and of applied physics and the Lee Otterson Professor in the School of Engineering, first started sequencing patients’ genomes at Stanford more than a decade ago.

“We imagined that someday, this sort of service would be much more broadly available — almost like getting a cholesterol test. It was a very futuristic thought,” Ashley said. “What we were building at that time was the foundation of this program.”

Ashley has seen the power of genome sequencing through his work in the Undiagnosed Diseases Network, a multisite study aimed at understanding mysterious illnesses, as well as at the Center for Inherited Cardiovascular Diseases, which he founded and directs.

Science has been slow to identify genes that cause some relatively common cardiovascular diseases, such as cardiomyopathy and arrythmia, both ailments that cause the heart muscle to malfunction, Ashley said. “These syndromes in cardiology are quite well recognized, but their molecular basis is not,” he said. “For every 100 cardiomyopathy patients, we only find a genetic basis for about 50.” That’s because there are common genes known to play a role in cardiomyopathy, but not all cardiomyopathies are attributable to errors in those genes.

Amy Hower fell into this category. In 2009, when she was 32, she and her husband were ready to start a family, but an unexpected diagnosis derailed their plans. Hower told her doctor about a rapid heartbeat she’d been experiencing. A workup revealed that she had cardiomyopathy, a disease that diminishes the ability of the heart to pump blood and can lead to heart failure. “It was a real shock, and not exactly ideal circumstances to start a family,” Hower said.

She wanted to know what was behind her diagnosis, something her doctor had not been able to discern. (If you’re wondering how a physician can diagnose a condition without knowing the cause, think of the doctor looking at a half-completed puzzle: Even with bits missing, he or she can still surmise what the puzzle depicts.) Knowing which gene was behind her disease could tell her if it would be passed on to her children; it could also inform a treatment choice.

She began a yearslong quest to understand the genetic roots of her disease. Her efforts were fruitless until she was referred to Stanford Health Care, where she met Ashley. A disease sleuth, Ashley took her case.

“It was clear to me that Dr. Ashley is not just a clinician; he doesn’t just want to treat the symptoms. He understood my passion for wanting to find answers,” Hower said. Through genome sequencing, Ashley was able to decipher the likely genetic variation causing her heart condition.

The variant is novel, meaning it isn’t a known culprit for cardiomyopathy. Does it indicate a higher risk for cardiac arrest? Or does it give rise to more manageable symptoms? No one knows. The variant did, however, help explain a cellular oddity that was causing Hower’s worrisome heart rhythms, and this knowledge guided Ashley toward therapies for Hower.

Despite the uncertainties, Hower took comfort in what she did know: She didn’t have a variant previously shown to be detrimental, and the possibility of having a variant that wouldn’t cause her or her children great harm was enough to give her the confidence to start a family. “The results I got were life-changing for me,” Hower said.

From patient care to discovery

The primary focus of the genome sequencing service will be enhancing patient care, Ashley said, but it contributes to genetic discovery, too. As more cardiovascular patients make use of the service, more will eventually find novel answers in their genome. As doctors find more novel variants in patients, the chance of identifying new genes behind certain diseases also increases. “It’s the power of numbers,” Ashley said. He’s hopeful that the rate of gene discovery will increase dramatically, and not just in cardiovascular care.

“It’s not uncommon that patients have multiple diseases in their lifetime, or a single disease with multiple systems involved,” he said. “Before whole genome sequencing, doctors would likely have to order multiple tests to look for different sets of genetic causes. Through whole genome sequencing, you can have one test and capture all of that information. For now, we’re starting with cardiovascular disease patients, and then we’ll expand the program into our cancer clinics, but the ultimate aim is to have this service running throughout Stanford Health Care.”

Originally published at Stanford Medicine News Center