Abstract
Although the perinatal lethal form1 of osteogenesis imperfecta (OI type II) occasionally results from large rearrangements within the genes encoding type I collagen2–5, most mutations are far more subtle. The complexity of the human collagen genes6 precludes cloning and sequencing each gene from every patient, and we have therefore developed an approach to localizing mutations at the protein level. We report here that cells cultured from 15 infants with OI type II synthesized both normal type I procollagen and a form that was unstable, poorly secreted and excessively modified. Abnormal procollagen from different strains was overmodified to different extents. The patterns of overmodification we observed are best explained by mutations that disrupt the Gly-X-Y sequence of proα chains, and thus alter the rate of propagation of triple helix from COOH-terminus to NH2-terminus7. As a consequence, a given mutation allows overmodification of all three chains in a molecule NH2-terminal to its position in the triple helix.
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Bonadio, J., Byers, P. Subtle structural alterations in the chains of type I procollagen produce osteogenesis imperfecta type II. Nature 316, 363–366 (1985). https://doi.org/10.1038/316363a0
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DOI: https://doi.org/10.1038/316363a0
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