Missense and silent mutations in COL2A1 result in Stickler syndrome but via different molecular mechanisms

Stickler syndrome due to mutations in COL2A1 is usually the result of premature termination codons and nonsense mediated decay resulting in haploinsufficiency of type II collagen. Here we present two missense mutations and one apparently silent mutation that each result in Stickler syndrome, but via different molecular mechanisms. One alters the translation initiating ATG codon. The second mutation is a unique glycine substitution in the minor collagen helix of the procollagen. To our knowledge a glycine substitution has not previously been reported in this region of fibrillar procollagens. The third mutation appears to be a silent change altering a GGC codon to GGT both for glycine, but use of a splicing reporter assay demonstrates that it results in missplicing and a shift in the reading frame.