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Digital Clubbing Explained

May 30th, 2008 Medgadget Editors News

Digital clubbing, a classic medical sign of chronic hypoxemia, first described by Hippocrates in patients with empyema, has now been explained on the molecular level. A group of clinicians at Leeds University realized that a genetic mutation in one of the genes responsible for the breakdown of PGE2 prostaglandin results in increased clubbing.
And the rest is history:

Prof Bonthron, Dr Chris Bennett of the Yorkshire Regional Genetics Service and their colleagues studied a group of patients suffering from inherited primary hypertrophic osteoarthropathy (PHO), a genetic disorder in which the finger clubbing is accompanied by painful joint enlargement and a thickening of the bone.
Their findings implicated a fatty compound called PGE2, which is produced naturally by the body to mediate the effects of internal inflammation. Crucially, once it has done its work, PGE2 is broken down by an enzyme 15-HPGD, produced in the lungs. The patients followed by the Leeds study were found to have a genetic mutation which prevented the production of 15-HPGD, resulting in up to ten times as much of the PGE2 in their systems.
"If you don’t have this enzyme the PGE2 isn’t broken down normally and simply builds up," said Bonthron, whose findings are published online this week in Nature Genetics.
In lung cancer patients, it is most likely overproduction of PGE2 by the tumour that causes the clubbing. In congenital heart disease, blood bypasses the lungs, where PGE2 is normally broken down by 15-HPGD.
The researchers have suggested that a straightforward urine test for levels of PGE2 may be a useful first step in the diagnosis of individuals with unexplained clubbing, and to understanding whether it is the symptom of something far more serious. The results also suggest that existing drugs such as aspirin, which are already used to prevent PGE2 production, may be effective in reducing the painful symptoms of finger clubbing.
It has taken 2,000 years to make the connection, but Bonthron adds: "Actually, when you look back, it’s rather obvious. When we found this gene, everything else fell neatly into place – it was like a smack on the forehead."

Press release: Leeds medics solve an ancient riddle — and offer new tool for diagnosis…
Abstract: Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy Nature Genetics 40, 789 – 793 (2008)

Medgadget Editors

Medical technologies transform the world! Join us and see the progress in real time. At Medgadget, we report the latest technology news, interview leaders in the field, and file dispatches from medical events around the world since 2004.

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