Gene Sequencing for Rare Diseases

For years, Tom Staniford has defied the odds, becoming a national cycling champion in Great Britain despite a debilitating illness.

Now, researchers have learned what's causing his symptoms—a rare genetic disorder known as MDP syndrome. According to Andrew Hattersley, a Wellcome Trust senior investigator at the University of Exeter Medical School in London, Staniford's condition may affect as few as eight people in the world.

The discovery, published today in Nature Genetics, may mean even more medals for Staniford. He is hoping the diagnosis will lead to him being reclassified for the 2016 Paralympic games in Rio de Janeiro, Brazil.

Currently, the International Cycling Union has placed Staniford in a class with athletes he believes have less serious disabilities. A reclassification would improve his chances of becoming a global champion.

“They are doing the best they can to ensure a level playing field, but due to so little being known about my condition and how it affects my functional cycling ability, I am currently placed in a class which I do not feel is fair,” Staniford told Healthline. “I simply want them to look at the new medical evidence, and the considered opinions of some of the most talented and respected medical professionals in the world, and perhaps reconsider my classification in light of these new findings.”

Hattersley has worked with Staniford for many years to help him manage his condition, which was once thought to be progeria, a disorder that causes extremely premature aging.

Staniford's symptoms have long been a riddle for doctors. Although he is physically fit, he is unable to store body fat beneath his skin and his body reacts as if he were obese because of higher-than-normal fat levels in his blood. As a result, he also has type 2 diabetes. During childhood, he lost all the fat around his face and limbs and developed hearing problems.

“[Staniford's case] helps us understand how some people can be 'fit fat' while others are very much 'unfit fat,'” Hattersley told Healthline.

The researchers looked at four unrelated patients in the United Kingdom, the U.S., and India. All had the same symptoms, and none had any family history of similar symptoms.

So, the scientists went looking for a small change in the 30 million base pairs that make up the DNA of the human genome. “The ability to look at 30 million bases in a single study, which takes under 48 hours, is a massive technological triumph,” Hattersley said. “If our genetic information is a library of books, the proof reader now reads the whole library of books in one go, not just a book at a time.”

The researchers found that Staniford and another patient had changes in their POLD1 gene, a key player in DNA replication. The changes were not inherited, but instead developed spontaneously. This genetic mutation caused a single amino acid to go missing from the enzyme the POLD1 gene codes for.

Staniford has never allowed his condition to stop him from being a professional pedaler. As recently as Sunday, he won a bicycle race by a wide margin.

The exercise he gets from cycling stimulates his body's insulin response, helping with his diabetes. He has been able to control his diabetes with the prescription medication Metformin.

Staniford's love of cycling began as a child while watching the Tour de France on television. “I used to love watching the fields of sunflowers on screen and the bright colors of the team kits,” he said.

He used to enjoy running, he said, but eventually his condition made it difficult because he lacks fat padding on the soles of his feet. “I missed the adrenaline buzz of endurance sports and the feelings of achievement you get from pushing your own boundaries,” Staniford said. “I started riding more and realized that I could get the same hit with less foot pain because cycling is, obviously, quite weight-bearing with the majority of time spent in the saddle.”

For Staniford, cycling keeps him feeling motivated and independent. “It feels good to be moving under your own effort, the feeling of 'I'm doing this,'” he said. “You have one life to live, and I'm intent on living mine."

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