A SINGLE-BASE MUTATION IN THE TYPE-II PROCOLLAGEN GENE (COL2A1) THAT CONVERTS GLYCINE ALPHA-1-247 TO SERINE IN A FAMILY WITH LATE-ONSET SPONDYLOEPIPHYSEAL DYSPLASIA

A search for mutations in the gene for type II procollagen (COL2A1) wa s carried out in a family with late onset spondyloepiphyseal dysplasia resulting in short stature, restricted mobility and severe pain in jo ints, deforming arthritis in the hips, and claudication. Analysis of t he HindIII and VNTR polymorphisms at the COL2A1 gene in the family rai sed the possibility that the gene cosegregated with the disease. Scree ning for mutations in the COL2A1 gene using PCR-denaturing gradient ge t electrophoresis suggested a sequence variation in exon 19 of one all ele of the COL2A1 gene in the proband. Direct sequencing of the PCR pr oducts for exon 19 revealed a single base mutation that converted the codon of -GGT- for glycine at alpha 1-247 to -AGT-, a codon for serine . The mutant COL2A1 allele was present in all affected family members, but absent in nonaffected members and in a group of 50 unrelated heal thy individuals. It was also absent in 20 unrelated patients with chon drodysplasias and 30 unrelated patients with early onset osteoarthriti s. (C) 1994 Wiley-Liss, Inc.