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Molecular Genetics of the Cartilage Collagenopathies

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Cartilage

Abstract

The cartilage extracellular matrix is rich in fibrillar- and fibril-associated collagens, and mutations in these collagen genes cause a wide range of chondrodysplasias, ranging from premature arthritis through to severe early lethal disorders. Collagen mutations can interfere with matrix organisation and cause cartilage dysfunction by reducing synthesis of structurally normal protein, or through protein misfolding which leads to intracellular retention and degradation, and consequent secretion of reduced amounts of structurally abnormal protein. In addition, collagen misfolding mutations can induce a cellular unfolded protein response which can alter chondrocyte differentiation and ultimately promote apoptosis and thus contribute to the pathology. The relative impact of intracellular and extracellular consequences is likely mutation and collagen type specific. Manipulating protein degradation pathways and unfolded protein response signalling offers hope for treating genetic chondrodysplasias.

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Authors and Affiliations

  1. Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, 3052, Australia

    Shireen R. Lamandé PhD, Trevor L. Cameron PhD, Ravi Savarirayan MD & John F. Bateman PhD

  2. Department of Paediatrics, University of Melbourne, Parkville, 3052, Australia

    Shireen R. Lamandé PhD & Ravi Savarirayan MD

  3. Victorian Clinical Genetics Service, Melbourne, Australia

    Ravi Savarirayan MD

  4. Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Parkville, 3052, Australia

    John F. Bateman PhD

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  1. Shireen R. Lamandé PhD
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  2. Trevor L. Cameron PhD
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  3. Ravi Savarirayan MD
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  4. John F. Bateman PhD
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Correspondence to Shireen R. Lamandé PhD .

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  1. Orthopädische Klinik für die Universität Regensburg, Universitätsklinikum Regensburg, Regensburg, Germany

    Susanne Grässel

  2. Department of General, Trauma, and Reconstruction Surgery, Ludwig-Maximilians-University, Munich, Germany

    Attila Aszódi

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Lamandé, S.R., Cameron, T.L., Savarirayan, R., Bateman, J.F. (2017). Molecular Genetics of the Cartilage Collagenopathies. In: Grässel, S., Aszódi, A. (eds) Cartilage. Springer, Cham. https://doi.org/10.1007/978-3-319-45803-8_6

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