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How genetic sequencing can unlock secret DNA mutations — and save lives

May 13, 2016 at 6:20 PM EDT
Every year, thousands of young people who seemed otherwise healthy die suddenly. The reason sometimes is long-rooted, secret gene mutations passed down through the generations. Doctors at the Scripps Translational Science Institute are using gene sequencing and “molecular autopsies” to uncover these hidden mutations and allow patients to take preventative action. David Wagner of KPBS reports.

JUDY WOODRUFF: Each year, thousands of seemingly healthy young people suddenly die. And, in many cases, doctors aren’t able to determine the cause.

Scientists in San Diego are starting to solve some of these medical mysteries through a process called genetic sequencing. What they’re learning can have a profound ripple effect on surviving family members.

Science reporter David Wagner from our member station KPBS in San Diego reports.

DAVID WAGNER: Dardie Robinson leads a typical life in Portland, Oregon. She spends her days working as a paralegal and catching up with all the kids she has raised.

But unknown to her, she was carrying a genetic mutation that left her and family members vulnerable to sudden heart failure. A year-and-a-half ago, she received an unexpected call. It was about her son, Daniel.

DARDIE ROBINSON, Mother: I got a call out of the blue from his girlfriend. And — sorry — she said that paramedics were there working on Daniel, that she had found him, that he was blue and unresponsive.

And I told her, I said, “Tell him his momma loves him.”

And she said, “Well, I’m sure he can’t hear you.”

I said, “Tell him anyway.”

And so she did.

DAVID WAGNER: In tears, she left the office and got in her car.

DARDIE ROBINSON: And on the way home, I got the call that there was nothing they could do, and that he was gone.

DAVID WAGNER: Daniel was 29 and otherwise healthy. No one knew why he had died so suddenly.

DARDIE ROBINSON: That was, to me, part of the — really the worst part, is because the word to us initially was, they thought that he must have committed suicide, he must have taken something. And I kept saying, that doesn’t make sense.

DAVID WAGNER: An autopsy pointed to problems with his heart. And while she was relieved suicide was ruled out, the autopsy left her unsettled.

If this could kill Daniel at 29, could it strike her other biological children?

DARDIE ROBINSON: That was the question. Is it going to happen again? Which one of my kids? Me? I’m OK if it’s me, but I’m not OK if it’s my kids.

DAVID WAGNER: Not long after she received the autopsy report, Dardie read a Los Angeles Times story about a study happening in San Diego.

Scientists at the Scripps Translational Science Institute were using gene sequencing to take another look at cases like her son’s. They wanted to perform what they called molecular autopsies.

Scripps research Ali Torkamani says one of the reasons they agreed to take on Daniel’s case was a strong family history of early heart failure.

ALI TORKAMANI, Geneticist, Scripps Translational Science Institute: The fact that there was more than one sudden death in the family at a young age sort of highlighted the point for us, this is likely a genetic issue.

DAVID WAGNER: Daniel, at 29, was by far the youngest.

DARDIE ROBINSON: So, this was my dad. He as in the Navy.

DAVID WAGNER: But a number of Dardie’s relatives had died from sudden heart failure in their 40s and 50s.

DARDIE ROBINSON: And then there’s little Mr. Daniel.

DAVID WAGNER: With strong clues that Daniel’s death may have been related to his DNA, the Scripps researchers sequenced genes from Daniel’s heart tissue. They also sequenced his parents’ genes.

ALI TORKAMANI: And that’s when we found this mutation in this gene, TRPM4.

DAVID WAGNER: Torkamani says mutations on this gene have been known to cause a disorder called progressive familial heart block. It short-circuits the heart’s electrical signals, eventually causing the heart to just stop beating.

ALI TORKAMANI: And it’s that mutation that we believe is the cause of sudden death in Daniel and in other family members.

DARDIE ROBINSON: “The mutation is likely to be positive for sudden death.”

DAVID WAGNER: The researchers found the same mutation in Dardie, who had passed it down to Daniel. And because it’s an autosomal dominant gene, there’s a 50 percent chance she passed it down to her other children too.

Scripps director Eric Topol oversees the study. He says Dardie’s case illustrates how a genetic discovery in cases like this can provide valuable, even lifesaving information to surviving family members.

DARDIE ROBINSON: There, he was brand-new, brand-new baby.

ERIC TOPOL, Director, Scripps Translational Science Institute: Because this is something that is eminently preventable with things like a defibrillator. So, whereas all these relatives through many generations had sudden death, we may be able to actually preempt this in the future.

DAVID WAGNER: Dardie is now considering getting a surgically implanted device to protect her heart from what happened to Daniel’s. She’s also on a mission to get relatives on her side of the family tested for the mutation.

DARDIE ROBINSON: Daniel did something significant. He gave us answers that will benefit not just dozens, but potentially, down the road, hundreds of people, maybe even thousands, because I don’t believe that this is just limited to my family.

DAVID WAGNER: Not every case Scripps looks at is this clear-cut. But the researchers say certain discoveries they’re making could end up preventing other sudden deaths.

If this new approach to autopsies becomes more common, researchers say, perhaps, in the future, fewer families will have to live with the pain of not knowing how their loved one died.

For the “PBS NewsHour,” I’m David Wagner in San Diego.