AUTOSOMAL-DOMINANT SPONDYLARTHROPATHY DUE TO A TYPE-II PROCOLLAGEN GENE (COL2A1) POINT MUTATION

Osteoarthrosis represents a very common disease with heterogeneous eti ology. In some pedigrees linkage of the condition with the type II col lagen gene (COL2A1) has been established, but information on the under lying gene defect is still incomplete as only one mutation causing thi s phenotype has been identified. We analyzed the COL2A1 gene in a 27-y ear-old woman and her 47-year-old mother presenting with severe premat ure osteoarthrosis and X-ray signs compatible with mild spondyloepiphy seal dysplasia. Examination of the complete gene in both patients was done by amplification of all 54 exons, screening of the PCR products b y SSCP-analysis, and subsequent sequencing. In mother and daughter a G to A transition at the 5'-end of exon 21 was detected, leading to a s ubstitution of serine for glycine at position 274 of the triple helica l domain. The mutation was not present in unaffected family members or in healthy control individuals. The autosomal dominant spondylarthrop athies may represent the less severe entities of the clinical spectrum of type II collagenopathies. (C) 1994 Wiley-Liss, Inc.