Clinical correlations of osteoarthritis associated with a single-base mutation (arginine super(519) to cysteine) in type II procollagen gene: A newly defined pathogenesis

• Published in: Arthritis and rheumatism 1994-02, Vol.37 (2), p.264-269
• Main Authors: Pun, Y L, Moskowitz, R W, Lie, S, Sundstrom, W R, Block, SR, McEwen, C, Williams, HJ, Bleasel, J F, Holderbaum, D
• Format: Article
• Language: English
• ISSN: 0004-3591
• DOI: 10.1002/art.1780370216

Sixty-six subjects from 7 families with a strong family history of generalized osteoarthritis (OA) and 13 patients with erosive OA were evaluated clinically and radiologically. Blood samples from 58 subjects in the familial OA group and from all 13 patients with erosive OA were obtained for DNA analysis. Exon 31 of COL2A1, which spans residue 519, was amplified by polymerase chain reaction. The arg super(519)-to-cys mutation was detected in 2 of the 7 families with generalized OA. In these 2 families, the mutation was present in the 2 probands and in 19 other clinically affected family members, as well as in 3 (so-far) clinically unaffected family members (ages 25, 14, and 11 years). It was absent in 18 clinically unaffected members tested. The mutation was associated with a distinctive pattern of early-onset, aggressive, generalized OA with a mild spinal chondrodysplasia. Inheritance was autosomal dominant. No mutation was found in any of the patients with erosive OA.