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: The technique of denaturing gradient gel electrophoresis was used to scan polymerase chain reaction (PCR) products from 45 exons and exon-flanking sequences of the COL2A1 gene in more than 70 patients with cartilage diseases whose severity ranged from mild to lethal. PCR products with abnormal migrations were then sequenced.
Results: Among the 3 patients with lethal hypochondrogenesis who were analyzed, all 3 were found to have a mutation in the COL2A1 gene. Among 17 patients with spondyloepiphyseal or spondyloepimetaphyseal dysplasia, 2 well-defined and 2 probable mutations were found. Among 15 patients with the Wagner-Stickler syndrome, 2 well-defined and 2 probable mutations were found. Among 45 patients with early-onset familial OA, 1 probable mutation was found.
Conclusion: Using the procedure developed for analysis of the COL2A1 gene, mutations were detected in > 20% of patients with chondrodysplasias and up to 2% of patients with early-onset familial OA. However, these percentages are only minimal estimates because all possible mutations in the gene cannot be detected with this procedure.