SPONDYLOEPIPHYSEAL DYSPLASIA AND PRECOCIOUS OSTEOARTHRITIS IN A FAMILY WITH AN ARG(75)-]CYS MUTATION IN THE PROCOLLAGEN TYPE-II GENE (COL2A1)

Direct sequencing of polymerase chain reaction (PCR)-amplified genomic DNA from a patient with spondyloepiphyseal dysplasia and precocious o steoarthritis revealed a single-base change in exon 11 of the type II procollagen gene (COL2A1), which produces an Arg--> Cys mutation in on e allele. The proband is a member of a large Chilean kindred presentin g with chondrodysplasia of the hips, knees, shoulders, elbows, and spi ne associated with severe, early-onset osteoarthritis. All affected in dividuals exhibit mildly short stature; in addition, five out of seven affected family members display shortened metacarpals or metatarsals. DNA from affected and unaffected family members was PCR-amplified and analysis of restriction digests of the products determined that the m utation segregated with the disease with a lod score of 2.2 at zero re combination. The mutation, which resides in the triple-helical region of type II procollagen at amino acid position 75, is the second exampl e of an Arg-->Cys mutation in the COL2A1 gene in heritable cartilagino us disease and is the first example of a point mutation in the amino t erminal region of the alpha1 (II) chain, that results in a spondyloepi physeal dysplastic phenotype.