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Tenascin–X deficiency is associated with Ehlers–Danlos syndrome

Nature Genetics volume 17, pages 104–108 (1997)Cite this article

Abstract

The tenascins are a family of large extracellular matrix proteins with at least three members: tenascin-X (TNX)1–3, tenascin-C (TNC, or cytotactin)4–6 and tenascin-R (TN-R, or restrict in)7,8. Although the tenascins have been implicated in a number of important cellular processes, no function has been clearly established for any tenascin9. We describe a new contiguous-gene syndrome, involving the CYP21B and TNX genes, that results in 21-hydroxylase deficiency and a connective-tissue disorder consisting of skin and joint hyperextensibility, vascular fragility and poor wound healing. The connective tissue findings are typical of the Ehlers-Danlos syndrome (EDS)10. The abundant expression of TNX in connective tissues2,11–13 is consistent with a role in EDS, and our patient's skin fibroblasts do not synthesize TNX protein in vitro or in vivo. His paternal allele carries a novel deletion arising from recombination between TNX and its partial duplicate gene, XA14, which precludes TNX synthesis. Absence of TNX mRNA and protein in the proband, mapping of the TNX gene and HLA typing of this family suggest recessive inheritance of TNX deficiency and connective-tissue disease. Although the precise role of TNX in the pathogenesis of EDS is uncertain, this patient's findings suggest a unique and essential role for TNX in connective-tissue structure and function.

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Authors and Affiliations

  1. Department of Pediatrics and Cardiovascular Research Institute, University of California–San Francisco, San Francisco, California, 94143, USA

    Grant H. Burch, Yan Gong, Wenhui Liu, Robert W. Dettman, Walter L. Miller & James Bristow

  2. Department of Metabolic Research Unit, University of California–San Francisco, San Francisco, California, 94143, USA

    Walter L. Miller

  3. Department of Medical Genetics, Valley Children's Hospital, Fresno, California, 93703, USA

    Cynthia J. Curry

  4. Department of Medicine, University of Washington School of Medicine, Seattle, Washington, 98195, USA

    Lynne Smith

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Correspondence to James Bristow.

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Burch, G., Gong, Y., Liu, W. et al. Tenascin–X deficiency is associated with Ehlers–Danlos syndrome. Nat Genet 17, 104–108 (1997). https://doi.org/10.1038/ng0997-104

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