A single base mutation in the type II procollagen gene (COL2A1) that converts glycine α1-247 to serine in a family with late-onset spondyloepiphyseal dysplasia

A search for mutations in the gene for type II procollagen (COLZA 1) was carried out in a family with late‐onset Spondyloepiphyseal dysplasia resulting in short stature, restricted mobility and severe pain in joints, deforming arthritis in the hips, and claudication. Analysis of the HindIII and VNTR polymorphisms at the COL2A1 gene in the family raised the possibility that the gene cosegregated with the disease. Screening for mutations in the COL2A1 gene using PCR‐denaturing gradient get electro‐phoresis suggested a sequence variation in exon 19 of one allele of the COL2A1 gene in the proband. Direct sequencing of the PCR products for exon 19 revealed a single base mutation that converted the codon of ‐GGT‐ for glycine at αl‐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 healthy individuals. It was also absent in 20 unrelated patients with chondrodysplasias and 30 unrelated patients with early‐onset osteoarthritis. © 1994 Wiley‐Liss, Inc.