An α1 II Gly913 to Cys substitution prevents the matrix incorporation of type II collagen which is replaced with type I and III collagens in cartilage from a patient with hypochondrogenesis
✍ Scribed by Mundlos, Stefan; Chan, Danny; McGill, Jim; Bateman, John F.
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 37 KB
- Volume
- 63
- Category
- Article
- ISSN
- 0148-7299
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✦ Synopsis
A heterozygous mutation in the COL2A1 gene was identified in a patient with hypochondrogenesis. The mutation was a single nucleotide transition of G3285T that resulted in an amino acid substitution of Cys for Gly9I3 in the al(I1) chain of type I1 collagen. This amino acid change disrupted the obligatory Gly-X-Y triplet motif required for the normal formation of a stable collagen triple helix and prevented the deposition of type I1 collagen into the proposita's cartilage, which contained predominantly type I and I11 collagens and minor amounts of type XI collagen. Biosynthetic analysis of collagens produced and secreted by the patient's chondrocytes cultured in alginate beads was consistent with the in vivo matrix composition, demonstrating that the main products were type I and I11 collagens, along with type XI collagen. The synthesis of the cartilage-specific type XI collagen at similar levels to controls indicated that the isolated cartilage cells had re-differentiated to the chondrocyte phenotype. The chondrocytes also produced small amounts of type I1 collagen, but this was post-translationally overmodified and not secreted. These data further delineate the biochemical and phenotypic consequences of mutations in the COL2A1 gene and suggest that cartilage formation and bone development can take place in the absence of type I1 collagen.