How One Woman Deciphered Her Own Genetic Mutation

Kim, meanwhile, disappeared down to Baja in Mexico. Gavrilova’s scepticism had worn her down and she fully expected that the results would come back negative.

When she returned home in May, there was a letter waiting for her. It was from Gavrilova. She had been trying to call for months. The test had come back positive: on one of her two copies of LMNA Goodsell had a mutation, in a part of the gene that almost never changes. LMNA consists of 57,517 DNA letters, and in the vast majority of people (and most chimps, monkeys, mice and fish) the 1,044th position is filled by a G (guanine). Kim had a T (thymine). “All evidence suggests that the mutation found in this patient might be disease-causing,” Gavrilova wrote in her report.

In other words, Kim was right.

“I’m beyond impressed,” says Michael Ackerman, a geneticist at the Mayo Clinic. He specializes in inherited heart disorders like ARVC that can cause sudden death at any time. Such diseases make for people who do their homework, but Ackerman describes most as “Google-and-go” patients who check their diagnosis online, or read up about treatment options. Kim had written up her research as a white paper—36 pages of research and analysis. “Kim’s the only one who handed me her own thesis,” he says. “Of all the 1,000-plus patients I’ve taken care of, none have done extensive detective work and told physicians which genetic test to order.”

He thinks she nailed it too. It is unlikely to be the whole story—Kim almost certainly has other mutations that are affecting the course of her disease—but LMNA “is certainly the leading contender for a unifying explanation, without there being a close second,” he says. “The evidence is pretty good for this being a smoking gun.”

The test had vindicated her hypothesis, but it also raised some confusing questions. Heart problems are a common feature of laminopathies, but those mutations had never been linked to ARVC, Kim’s specific heart malfunction. Had she been misdiagnosed? A few months later, Kim stumbled across a new paper by a team of British researchers who had studied 108 people with ARVC and found that four had LMNA mutations (and none of the standard ones). “To the best of our knowledge, this is the first report of ARVC caused by mutations in LMNA,” they wrote. They didn’t know about Kim’s work—they couldn’t have, of course. But she knew. Kim had beaten them to it. “I was so excited, I was running up and down the beach,” she says.

* * *

When patients get solutions to their own genetic puzzle, it’s always professional geneticists who do the solving. Take James Lupski. He has been studying Charcot-Marie-Tooth for decades, and discovered the first gene linked to the condition. He also has it himself. In 2010 he sequenced his own genome and discovered a previously unidentified mutation responsible for the disease. In other cases anxious parents have been instrumental in uncovering the causes of their kids’ mysterious genetic disorders after long diagnostic odysseys, but only by bringing their cases in front of the right scientists.

Kim, however, was an amateur. And to her, sequencing was not a Hail Mary pass that would—maybe, somehow—offer her answers; it was a way of confirming a carefully researched hypothesis. “People have been talking about empowering consumers since there was an Internet,” says Eric Topol, a geneticist at the Scripps Clinic. “But finally, we’ve reached a point where someone can delve into their condition beyond what the top physicians at the Mayo Clinic could. They couldn’t connect the dots. She did.”

Topol, a self-described “digital medicine aficionado,” argues that Kim is a harbinger of things to come. In his book The Creative Destruction of Medicine, Topol foretells a future where doctors are no longer the gatekeepers of medical information. Advances like personal genetic testing or sensors that measure molecules in the blood will give patients the power to better understand themselves and to exercise more control over their healthcare. Medicine is becoming more democratic.

Kim is a vanguard of that change. She lacked academic knowledge, but she had several advantages over her physicians and other researchers in the field. She had detailed first-hand knowledge of her own symptoms, allowing her to spot connections in the scientific literature that others had missed. She could devote hours to learning everything about her niche disorders—time and focus that no clinician could reasonably spend on a single case. And she had unparalleled motivation: “There’s nothing that engages your curiosity more than being confronted by your death,” she says.

It is also becoming ever easier for that curiosity to lead to discovery. In the past geneticists would try to diagnose patients by looking at their medical history and deciding which genes might be worth sequencing, as Gavrilova tried to do for Kim. The approach makes sense, but it only ever confirms known links between genes and diseases.

One way of finding new links is to sequence a patient’s exome—the one percent of their genome that contains protein-coding genes. It’s cheaper than sequencing a full genome, but allows researchers to hunt for disease-related genes by interrogating every possible suspect simultaneously, without having to whittle down the list first. “Suddenly, we’re finding patients presenting with Disease X who have mutations in genes never previously associated with that disease,” says Daniel MacArthur, a geneticist at Massachusetts General Hospital. “That’s happening in nearly every disease field right now.”

Exome sequencing is now barely more expensive than sequencing much narrower gene panels. MacArthur says that the cost has already fallen below $1,000 and may halve again this year. And once patients have that information, they could use it to find others with the same mutations and check if they have the same symptoms.

Currently, the results from DNA sequencing studies are largely squirreled away in boutique databases that collate mutations for specific diseases or genes. The ironically named Universal Mutation Database covers mutations in only 34 genes, including LMNA. Broader ones exist, but for decades they have been incomplete, rife with mistakes, or inaccessible, even to other researchers—a sad state of affairs that MacArthur laments as the “single greatest failure in human genetics.” Now, though, the National Institutes of Health are developing an open database called ClinVar that covers all disease mutations. “A lot of us are putting our hopes on this,” says MacArthur. “We need to come up with resources that empower people to make surprising links, which is hard to do if the data are broken up by disease or gene.”

But for every Kim, there are others who research their own conditions and come up with wrong answers.

In one study four non-specialist volunteers tried to diagnose 26 cases from the New England Journal of Medicine by Googling the symptoms. They got less than a quarter right. Genetic diseases arguably lend themselves to confusion and misinformation. They are often both debilitating and enigmatic, and getting sequenced can offer little comfort beyond a diagnosis. If mainstream science has no easy answers to offer, many patients will follow any lead, no matter how weak. “There’s a tendency for people to spin very convoluted stories on tenuous threads of evidence. Even scientists do that,” says MacArthur. “I have heard of a lot of rare-disease patients who come up with hypotheses about their disease, and very few turn out to be correct.”

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Ed Yong

Ed Yong is a science writer based in London.

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