Scientific Method / Science & Exploration

DIY diagnosis: How an extreme athlete uncovered her genetic flaw


Learning the language

But Kim was never one for relying on others. She tried a support group when she got her implant, but it did nothing for her. She dipped her toes in patient forums, but she was always frustrated by the rampant misinformation. “People just weren’t interpreting things correctly,” Kim says. “I wanted more rigor.”



“Kim has an incredible ability to understand the genetic literature,” says Martha Grogan, a cardiologist from the Mayo Clinic and an old friend of CB’s who now coordinates Kim’s care. “We have a lot of patients who ask great questions, but with Kim, it’s like having another research fellow.”


Enlarge / Teased sciatic nerve fibers triple labeled for neurofilament (blue), S100 (red), and DRP2 (green). The S100 protein is expressed in the Schwann cells of the peripheral nervous system and in astroglial cells of the central nervous system. DRP2 (dystrophin-related protein) is thought to be involved in membrane-cytoskeleton interactions at sites of membrane specialization and intercellular contact in various tissues. Disruption of these protein complexes are thought to be a cause of Charcot-Marie-Tooth disease.

Kim looked at every gene linked to Charcot–Marie–Tooth—there are more than 40 overall, each one imparting a slightly different character to the disease. One leapt out: LMNA, which codes for a group of rope-like proteins that mesh into a tangled network at the center of our cells. This ‘nuclear lamina’ provides cells with structural support, and it interacts with a bunch of other proteins to influence everything from the packaging and activation of genes to the suicide of damaged cells. Given this central role, it makes sense that mutations in LMNA are responsible for at least 15 different diseases, more than any other human gene. These laminopathies comprise a bafflingly diverse group—nerve disorders (like Charcot–Marie–Tooth), wasting diseases of fat and muscle, and even premature aging.


She also saw a heart disorder linked to the LMNA gene that wasn’t ARVC but which doctors sometimes mistake for it. “Everything was encapsulated,” she says. “It was like an umbrella over all of my phenotypes. I thought: this has to be the unifying principle.”



Gavrilova pushed Kim toward a different test that would look at seven genes linked to ARVC. Her insurance would cover that, but if she insisted on sequencing the DNA of her LMNA gene, she would have to foot a $3,000 bill herself. Why waste the money, when it was such an unlikely call? But Kim was insistent. She knew that the known ARVC genes explain only a minority of cases and that none of them was linked to neural problems. In all her searching, she had found only one that covered both her heart and nervous problem. Eventually, Gavrilova relented.

Kim, meanwhile, disappeared down to Baja in Mexico. Gavrilova’s skepticism 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.”


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