– San Jose Mercury News

When a 19-year-old engineering student was found dead in his bed in Yardley, Pa., his family was devastated. But when a conventional autopsy of the apparently healthy young man offered no answers, his parents were gripped by another medical concern: Could a silent but deadly condition be hiding in other members of the family?

Scientists at the Stanford University School of Medicine are on a quest to find out, searching samples of Richie Quake’s tissue for genetic clues that might explain why his heart suddenly stopped.

The “molecular autopsy” is believed to be the first time whole-genome sequencing has been used to seek a cause of death, although the Stanford team has used more focused genetic scans to investigate 17 other unexplained deaths.

Dr. Euan Ashley and his medical research team are scanning Quake’s DNA for errors that might cause irregular beating of the heart, invisible during traditional dissection.

NEW WAYS TO FIND ANSWERS

“We’re applying new technologies to an age-old practice, trying to work out why someone died, after they died,” said Ashley, who directs Stanford’s Center for Inherited Cardiovascular Disease.

“Because so many of these conditions can be familial, it becomes more important for surviving relatives,” he said. “This has the opportunity to save lives.”

The team’s data are still under analysis and their conclusions won’t be published until later this year. But they say they are zeroing in on a set of suspect gene mutations linked to faulty electrical signaling in a beating heart, a rare, poorly understood cause of sudden cardiac death.

If confirmed, the genomes of surviving relatives could be searched for similar flaws, and their health monitored closely.

‘I NEED YOU TO SAVE EVERYTHING’

Richie Quake seemed to be in perfect health. It was a morning three years ago when the black belt in karate lingered in bed because he felt chilly. Later that day, the Drexel University student was scheduled to work at a nearby theme park, dressed in a Big Bird costume.

“I kissed him good night the night before when he gave me a shirt for my birthday,” his father, Richard, told Stanford Medicine magazine. “My wife talked to him that morning. She said ‘OK, I love you,’ and she kissed him goodbye.”

After an autopsy, the coroner blamed a fluttering heart, or arrhythmia. But that’s a symptom, not a cause.

Richie’s father insisted the coroner collect both blood and tissue samples. “I told him, ‘I need you to save everything you possibly can for future testing,’” Richard Quake, a sales manager for an auto auction website, told Stanford Medicine.

Encouraged by cousin Stephen Quake, a Stanford bioengineering professor, Richard Quake sent tissue samples to Stanford.

LOOKING FOR KILLER GENES

Such cardiac death is generally linked to a problem in the pumping heart. The heart operates on electrical impulses that rhythmically stimulate the vessels, so blood can be pumped to the body. These electrical impulses are controlled by pores called “ion channels.” Death can occur when the proteins for these ion channels misfunction.

Stanford is not the only research facility searching, post-mortem, for killer genes. In Canada, a molecular autopsy of a 21-year-old student found a mutation that causes a heart problem called Long QT syndrome. Her mother was found to have the same mutation.

At Minnesota’s Mayo Clinic, Dr. Michael Ackerman has performed molecular autopsies of 49 young people who died suddenly. In seven cases, he found suspect mutations in a gene called RyR2, which regulates the influx of calcium into heart cells.

The Stanford team has used powerful computers to scan all 6 billion nucleotide letters in Richie’s genome, focusing on regions that regulate proteins in the heart muscle. So far they have identified 200 genetic variants in the young man’s genome, many never before associated with disease. Which one was lethal? That’s what the Stanford scientists hope to learn.