Paralympic cyclist's rare condition diagnosed with gene sequencing

The genetic mutation behind a UK paracyclist's mystery condition has been identified by an international team of scientists.

Tom Staniford, 2011 national paracycling champion, has no protecting fat on his body, suffers from extremely sore feet and is at a high risk of breaking bones if he falls from his bike. Despite the lack of fat, he has type 2 diabetes, which is typically associated with obesity, and has also used hearing aids since childhood.

Staniford, 23, did not know what was causing his symptoms, but a team led by the University of Exeter has sequenced his genome to diagnose the disorder and find the gene mutation responsible. He was found to have mandibular hypoplasia, deafness and progeroid features (MDP) syndrome, a rare condition thought to affect as few as eight people in the world.

The study was led by Professor Andrew Hattersley, who has been working closely with Staniford for several years to help manage and understand his condition. His team sequenced and compared the entire genomes of four unrelated patients in the UK, US and India who all had the same symptoms but did not have a family history of a similar condition. This suggested that their condition may have been caused by individual genetic mutations rather than inherited mutations.

They identified a missense mutation in the POLD1 gene on chromosome 19, which affects the activity of DNA polymerase, an enzyme crucial to DNA replication. The researchers suspect that this mutation is responsible for MDP syndrome in Staniford and the three other patients studied.

Although Staniford has found ways to manage his symptoms, the discovery may help in his bid to participate in the Rio 2016 Paralympic Games.

'In some ways, identifying the syndrome behind my symptoms shouldn't be important - a name is just a name, after all - but it is reassuring to know that there are other people with the condition and that we can lead relatively normal lives', says Staniford.

'What could prove crucial, though, is enabling me to be properly classified in competitions so that I am not competing at an unfair disadvantage against others. I hope to be able to compete for Great Britain in the 2016 Paralympics and this finding could make a real difference to my chances'.

Professor Hattersley said: 'Tom's condition has been a puzzle to us for many years. We could see the symptoms, including the very unusual case of type 2 diabetes in someone with no obvious body fat, but did not know what was causing them'.

'Identifying the gene responsible has implications both for predicting the long term impact of the condition on Tom's health and — equally importantly to him — on his sporting career'.