Widely distributed mutations in the COL2A1 gene produce achondrogenesis type II/hypochondrogenesis

The COL2A1 gene was assayed for mutations in genomic DNA from 12 patients w ith achondrogenesis type II/hypochondrogenesis, The exons and flanking sequ ences of the 54 exons in the COL2A1 gene were amplified by a series of spec ific primers using PCR. The PCR products were scanned for mutations by conf ormation sensitive gel electrophoresis, and PCR products that generated het eroduplex bands were then sequenced. Mutations in the COL2A1 gene were foun d in all 12 patients. Ten of the mutations were single base substitutions t hat converted a codon for an obligate glycine to a codon for an amino acid with a bulkier side chain. One of the mutations was a change in a consensus RNA splice site. Another was an 18-base pair deletion of coding sequences. The results confirmed previous indications that conformation sensitive gel electrophoresis is highly sensitive for detection of mutations in large an d complex genes. They also demonstrate that most, if not all, patients with achondrogenesis type II/hypochondrogenesis have mutations in the COL2A1 ge ne. Am. J. Med. Genet. 92:95-100, 2000, (C) 2000 Wiley-Liss, Inc.