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Genetics
Gene Found for Rare Bone Disorder
Researchers from the HSDM and Forsyth Institute joint Department of Oral Biology have discovered a genetic mutation responsible for cherubism, a childhood bone disorder. In its mild forms, cherubism causes children to develop chubby cheeks and upward-looking eyes like those of a cherub.
The discovery, reported in the June Nature Genetics, may lead to potential therapies or prenatal diagnosis for the disorder, said Bjorn Olsen, chair of the HSDM–Forsyth department. The findings also provide clues to the mechanisms underlying such bone-degrading disorders as osteoporosis, according to Ernst Reichenberger, an HSDM instructor in the department. He and Olsen led the research team, which included HSDM research fellow Yasuyoshi Ueki, first author on the paper.
The mutation affects primarily young children starting at age 3 or 4, when secondary teeth develop inside the jawbones. "At that time, there is much bone degradation and remodeling going on," Reichenberger said. But in cherubism, "there must be something wrong with the way certain bone cells receive information from other cells or extracellular matrix."
Ernst Reichenberger (above), Bjorn Olsen, Yasuyoshi Ueki, and colleagues found a rare bone disorder gene that may contribute to understanding and treating more common bone diseases. Photo by Graham Ramsay
In its severe forms, cherubism can lead to excessive degradation of the jawbone. The bone tissue is replaced by soft tissue masses that cause swelling of the face and can intrude into the eye socket and force the eyeballs to tilt upwards. Cherubistic patients also suffer from chronic inflammation of lymph nodes and tooth malformation and loss. Many have difficulty chewing because of reduced jaw movement.
The mutation leading to cherubism appears to affect a signaling mechanism that causes both bone-degrading osteoclasts and bone-building osteoblasts to function abnormally, Reichenberger said. Because no epidemiologic studies have yet been conducted, it is not known how many people have the disorder in addition to the approximately 200 reported in the medical literature.
Discovery of the mutant gene is a significant step in understanding the signaling process in bone cells and could yield important clues about the development of secondary teeth, Olsen said. By comparing the faulty signaling exhibited in cherubism with normal signaling, it may be possible to pinpoint crucial mechanisms for bone remodeling. This knowledge, the researchers hope, will contribute to methods for treating or averting cherubism and could one day allow prenatal diagnosis.
Even more important, however, is that understanding the signaling mechanisms exhibited in cherubism could lead to deeper knowledge and treatment of bone diseases that affect large segments of the worldÕs population. Among these are osteoporosis and its converse, osteopetrosis.
—Anita Harris
Copyright 2001 by the President and Fellows of Harvard College
