hand.
clubbed fingers can provide clues to other disorders.
Ann McGrath
club-shaped fingers may be a warning sign for serious heart and lung disease, but the cause of the disease remained a mystery for more than 2400 years. Now researchers may have taken a step toward solving the puzzle by identifying the mutation that grows a rare type of clubbing.
Clubbing, or swelling of the fingers, is one of the first symptoms of medical students learn to look for because it can signal lung cancer, heart disease, or other conditions serious. The father of medicine himself, Hippocrates, first described clubbing about 450 BCE, but researchers have yet to understand what triggers swelling.
Seeking a genetic index, a team led by David Bonthron, a clinical geneticist at the University of Leeds, UK, went to get the DNA glitch behind primary OAH (PHO). The rare, representing only 3% to 5% of clubbing, resulting in the end of the extended fingers and joint pain, but does not cause the other underlying disorders - although some patients also develop heart disease
team Bonthron. scanned the genomes of six PHO patients from three different families and found that they all had a mutation in the HPGD gene. The gene encodes an enzyme that breaks down prostaglandins, hormonelike molecules that promote inflammation and help regulate water balance and blood circulation - a process that could affect clubbing. Further examination showed that the patients had levels of PGE2 prostaglandin called higher than normal, confirming that the mutation leads to a defective enzyme that does not break down properly prostaglandins, the researchers report this week Nature Genetics . The discovery suggests that a urine test for elevated prostaglandin levels could help doctors diagnose this type of clubbing and that the condition could be reversed with existing drugs that block prostaglandins.
The overproduction of prostaglandins may also be the cause of the disco associated with lung cancer, heart disease and other diseases, said Bonthron. Although patients with these conditions have no HPGD mutation, he said, other aspects of their conditions, such as tumors that occur with lung cancer, trigger an increase in prostaglandins.
Manuel Martinez-Lavin, rheumatologist at the National Institute of Cardiology in Mexico City, Mexico, agreed that the discovery could offer insight into the cause of other forms of clubbing. But he doubts that high prostaglandins directly produce finger swelling. Indeed, the compounds were used to treat peptic ulcers, and there is no evidence of abnormalities of the fingers in these patients, he noted.
Instead, says Martinez-Lavin, high levels of prostaglandins could somehow afford another molecule called vascular endothelial growth factor (VEGF) to cause the disco. Previous studies have shown that PHO patients have high levels of VEGF, which can trigger symptoms of clubbing, including fluid accumulation, he said.
Related Sites
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- Learn more about primary OAH
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