The researchers uncovered two mutations involving the FRZB ("frisbee") gene located on chromosome 2, which has been implicated in familial osteoarthritis. In previous laboratory studies done elsewhere, FRZB appears to be important in the development of human limbs at a young age. Although the finding of the mutation in both affected and unaffected family members makes the mutation in and of itself insufficient to cause the clinical syndrome, it may play a role in what could be a polygenic trait.
"Further studies defining the genetic mutation related to chondrolysis seen in the family we reported have the potential not only for providing targets for approaches to treatment in the family, but may provide important information as to mechanisms of cartilage degeneration seen in the millions of individuals who suffer from primary osteoarthritis," said Roland Moskowitz, M.D., one of the investigators and a professor of medicine at Case and UHC. "The known relationship of the FRZB gene to embryonic skeletal development, and the observation by others that women with hip osteoarthritis have an increased frequency of this gene add to the significance of our observations," said Moskowitz, a leading expert on osteoarthritis.
The researchers made the findings after screening seven families with familial osteoarthritis looking for specific gene mutations. They discovered a family referred from elsewhere wherein the father, two daughters and a son have hereditary chondrolysis. In the family, this disease was so pronounced that the cartilage peeled off the bone, affecting mostly the shoulders, hips and knees. Several affected members of the family developed osteoarthritis in their first decade of life, and needed joint replacement by the time they reached their 20s. The youngest child underwent several arthroscopic procedures beginning at 16. The middle sibling needed a complete hip arthroplasty by age 26, and a second hip replacement less than two years later.
The lead author of the report is Daniel Holderbaum, Ph.D., senior research associate in Moskowitz's laboratory.