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Researchers find gene that creates ‘second skeleton’
The finding may lead to a drug treatment for fibrodysplasia ossificans progressive.
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Scientists discovered a mutant gene that triggers the body to form a “second skeleton,” also known as fibrodysplasia ossificans progressive, a rare disease that imprisons children in bone.
The research findings, published in the online edition of Nature Genetics, may one day lead to the development of a drug to not only to treat this rare bone disorder, but also to manage the more common bone buildup related to head and spine trauma, the researchers said.
“Fibrodysplasia ossificans progressive (FOP) bone is perfectly normal in every way, except it should not be there,” said Frederick Kaplan, MD, an orthopedist whose team at the University of Pennsylvania School of Medicine in Philadelphia pinpointed the cause of FOP.
Early in childhood, painful swellings, often mistaken for tumors, seize the skeletal muscles and transform them into bone. Attempts to remove the extra bone can lead to explosive growth of new bone. Even the slightest trauma such as bumps, bruises, childhood immunizations and injections for dental work can cause the muscles to turn to bone, researchers said.
Based on a single mutation
After 15 years of studying the genetic makeup of multigenerational families around the world, scientists at Penn’s Center for Research in FOP and Related Disorders found that the condition is caused by a single mutation in the Activin Receptor Type IA (ACVR1) gene. This means that tendons, ligaments and skeletal muscle begin painfully transforming into bone, sometimes locking joints overnight.
The genetic twist that leads to FOP ultimately impacts every condition affecting the formation of bone and every condition that plays a role in skeletal formation, he said.
Kaplan, geneticist Eileen M. Shore, and colleagues reported the research in Nature Genetics with contributions from researchers in Australia, Brazil, France, Germany, Great Britain, the Netherlands and South Korea.
The researchers believe it is possible to develop a drug that would block or bypass the genetic trigger of the extra bone growth. Eventually, it might block the unneeded bone that occasionally forms after hip replacement surgery.
“In the next five years, this might open up the possibility of developing drugs that would be effective in stopping bone formation,” said Victor A. McKusick, MD, professor of medical genetics at Johns Hopkins University School of Medicine in Baltimore.
He said the FOP genetic breakthrough is also likely to shed light on other related diseases.
For more information:
- Shore EM, Xu M, Feldman GJ, et al. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nature Genetics. 2006;38:525-527.