IDENTIFICATION OF COL2A1 GENE-MUTATIONS IN PATIENTS WITH CHONDRODYSPLASIAS AND FAMILIAL OSTEOARTHRITIS

Objective, To use a recently developed procedure for analysis of blood leukocyte DNA to detect mutations in the gene for type II procollagen (COL2A1) in patients with cartilage diseases ranging from early-onset familial osteoarthritis (OA) to lethal chondrodysplasias. Methods. Th e technique of denaturing gradient gel electrophoresis was used to sca n polymerase chain reaction (PCR) products from 45 exons and exon-flan king sequences of the COL2A1 gene in more than 70 patients with cartil age diseases whose severity ranged from mild to lethal. PCR products w ith abnormal migrations were then sequenced. Results. Among the 3 pati ents with lethal hypochondrogenesis who were analyzed, all 3 were foun d to have a mutation in the COL2A1 gene. Among 17 patients with spondy loepiphyseal or spondyloepimetaphyseal dysplasia, 2 well-defined and 2 probable mutations were found. Among 15 patients with the Wagner-Stic kler syndrome, 2 well-defined and 2 probable mutations were found. Amo ng 45 patients with early-onset familial OA, 1 probable mutation was f ound. Conclusion. Using the procedure developed for analysis of the CO L2A1 gene, mutations were detected in >20% of patients with chondrodys plasias and up to 2% of patients with early-onset familial OA. However , these percentages are only minimal estimates because all possible mu tations in the gene cannot be detected with this procedure.