MUTATION IN TYPE-II PROCOLLAGEN (COL2A1) THAT SUBSTITUTES ASPARTATE FOR GLYCINE ALPHA-1-67 AND THAT CAUSES CATARACTS AND RETINAL-DETACHMENT- EVIDENCE FOR MOLECULAR HETEROGENEITY IN THE WAGNER SYNDROME AND THESTICKLER SYNDROME (ARTHROOPHTHALMOPATHY)

A search for mutations in the gene for type II procollagen (COL2A1) wa s carried out in affected members of a family with early-onset catarac ts, lattice degeneration of the retina, and retinal detachment. They h ad no symptoms suggestive of involvement of nonocular tissues, as is t ypically found in the Stickler syndrome. The COL2A1 gene was amplified with PCR, and the products were analyzed by denaturing gradient gel e lectrophoresis. The results suggested a mutation in one allele for exo n 10. Sequencing of the fragment demonstrated a single-base mutation t hat converted the codon for glycine at position alpha1-67 to aspartate . The mutation was found in three affected members of the family avail able for study but not in unaffected members or 100 unrelated individu als. Comparison with previously reported mutations suggested that muta tions introducing premature termination codons in the COL2A1 gene are a frequent cause of the Stickler syndrome, but mutations in the COL2A1 gene that replace glycine codons with codons for bulkier amino acid c an produce a broad spectrum of disorders that range from lethal chondr odysplasias to a syndrome involving only ocular tissues, similar to th e syndrome in the family originally described by Wagner in 1938.