Get access

Extracellular matrix and platelet function in patients with musculocontractural Ehlers–Danlos syndrome caused by mutations in the CHST14 gene

Authors

  • Roberto Mendoza-Londono,

    Corresponding author
    1. Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada
    2. The Bone Health Centre, The Hospital for Sick Children, Toronto, Ontario, Canada
    • Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1H4.
    Search for more papers by this author
  • David Chitayat,

    1. Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada
    2. The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Walter H.A. Kahr,

    1. Division of Haematology/Oncology, Program in Cell Biology, The Hospital for Sick Children, Departments of Paediatrics & Biochemistry, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Aleksander Hinek,

    1. Division of Cardiovascular Research, Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Susan Blaser,

    1. Diagnostic Imaging, Division of Neuroradiology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Lucie Dupuis,

    1. Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada
    2. The Bone Health Centre, The Hospital for Sick Children, Toronto, Ontario, Canada
    Search for more papers by this author
  • Elaine Goh,

    1. Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Ramses Badilla-Porras,

    1. Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Andrew Howard,

    1. Department of Orthopedic Surgery, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
  • Laureane Mittaz,

    1. Division of Molecular Pediatrics, CHUV, Lausanne, Switzerland
    Search for more papers by this author
  • Andrea Superti-Furga,

    1. Division of Molecular Pediatrics, CHUV, Lausanne, Switzerland
    Search for more papers by this author
  • Sheila Unger,

    1. Division of Molecular Pediatrics, CHUV, Lausanne, Switzerland
    Search for more papers by this author
  • Gen Nishimura,

    1. Department of Pediatric Imaging, Tokyo Metropolitan Children's Medical Center, Fuchu, Tokyo, Japan
    Search for more papers by this author
  • Luisa Bonafe

    1. Division of Molecular Pediatrics, CHUV, Lausanne, Switzerland
    Search for more papers by this author

  • How to Cite this Article: Mendoza-Londono R, Chitayat D, Kahr WHA, Hinek A, Blaser S, Dupuis L, Goh E, Badilla-Porras R, Howard A, Mittaz L, Superti-Furga A, Unger S, Nishimura G, Bonafe L. 2012. Extracellular matrix and platelet function in patients with musculocontractural Ehlers–Danlos syndrome caused by mutations in the CHST14 gene. Am J Med Genet Part A. 158A:1344–1354.

  • The authors have no conflict of interest to declare.

Abstract

We report on a consanguineous, Afghani family with two sisters affected with characteristic facial features, multiple contractures, progressive joint and skin laxity, hemorrhagic diathesis following minor trauma and multisystem fragility-related manifestations suggestive of a diagnosis of musculocontractural Ehlers–Danlos syndrome (EDS). This novel form of connective tissue disorder was recently reported in patients of Japanese, Turkish, and Indian descent who were formerly classified as having EDS type VIB and has now been recognized to be a part of spectrum including patients previously classified as having adducted thumb-clubfoot syndrome. We identified a previously unreported mutation in the CHST14 gene, which codes for the enzyme dermatan 4-O-sulfotransferase. We discuss the prenatal presentation, detailed clinical manifestations, and neurological findings in two sisters with this newly described musculocontractural EDS-CHST14 type. We demonstrate that fibroblasts from one of our patients produce more chondroitin sulfate than normal and show lower than normal deposition of collagens I and II and fibrillin 1-containing microfibrills. These findings suggest that the imbalance in the glycosaminoglycan content in developing tissues might interfere with normal deposition of other extracellular matrix components and ultimately contribute to the development of the phenotype observed in these patients. Furthermore, we ruled out the contribution of intrinsic platelet factors to the bleeding diathesis observed in some affected individuals. © 2012 Wiley Periodicals, Inc.

Ancillary