Geneticists to arthritics: a gene's the rub.

Geneticists to arthritics: A gene's the rub

An inherited form of premature arthritis sometimes results from a minor typographical error in the genetic code for a joint-cushioning protein, according to new research. The disease, called primary osteoarthritis, can start to affect victims in their second or third decades of life, leaving them hobbled by midlife with limited, painful joint movement in the elbows, knees, hips and fingers.

Scientists estimate that as many as 6 million arthritic Americans can blame their disability at least in part on defective DNA, but they remain unsure how many of these people bear the newly pinpointed genetic glitch. Although the investigators found the mutation in all nine arthritic individuals of the one family they thoroughly studied, they note that other families with a history of the disease may harbor different genetic misspellings. But if the defect causes a large proportion of cases, its discovery could help clinicians identify people who have inherited the faulty gene, allowing early intervention.

Darwin J. Prockop of the Jefferson Medical College in Philadelphia and his colleagues examined DNA 19 individuals spanning three generations of a family with a propensity for primary osteoarthritis. Affected family members harbored an identical error within a gene on chromosome 12, they report in the September PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (Vol.87, No. 17). The gene contains instructions to make Type II procollagen -- the precursor of Type II collagen, which is the major ingredient of joint-surface protective linings. The gene was normal in all 10 unaffected family members and in 57 other unaffected people tested. Studies of 10 other families with inherited osteoarthritis remain largely inconclusive.

The researchers suggest that the mutation ultimately weakens collagen's triple-helical structure, making it susceptible to degeneration after only a few decades of normal wear and tear.

Although no effective drug therapy so far exists, Prockop says early detection of the faulty gene could help people "tailor their careers and exercise habits" to minimize arthritis-accelerating stresses.