Tenascin-X deficiency is associated with Ehlers-Danlos syndrome

Grant Burch, Yan Gong, Wenhui Liu, Robert W. Dettman, Cynthia J. Curry, Lynne Smith, Walter L. Miller, James Bristow

Research output: Contribution to journalArticle

244 Citations (Scopus)

Abstract

The tenascins are a family of large extracellular matrix proteins with at least three members: tenascin-X (TNX), tenascin-C (TNC, or cytotactin) and tenascin-R (TN-R, or restrictin). Although the tenascins have been implicated in a number of important cellular processes, no function has been clearly established for any tenascin. We describe a new contiguousgene 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). The abundant expression of TNX in connective tissues 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, XA, 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.

Original languageEnglish (US)
Pages (from-to)104-108
Number of pages5
JournalNature Genetics
Volume17
Issue number1
DOIs
StatePublished - 1997
Externally publishedYes

Fingerprint

Ehlers-Danlos Syndrome
Tenascin
Connective Tissue
tenascin X
Duplicate Genes
Histocompatibility Testing
Skin
Connective Tissue Diseases
Extracellular Matrix Proteins
Wound Healing
Genetic Recombination
Genes
Blood Vessels
Proteins
Fibroblasts
Joints
Alleles

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Burch, G., Gong, Y., Liu, W., Dettman, R. W., Curry, C. J., Smith, L., ... Bristow, J. (1997). Tenascin-X deficiency is associated with Ehlers-Danlos syndrome. Nature Genetics, 17(1), 104-108. https://doi.org/10.1038/ng0997-104

Tenascin-X deficiency is associated with Ehlers-Danlos syndrome. / Burch, Grant; Gong, Yan; Liu, Wenhui; Dettman, Robert W.; Curry, Cynthia J.; Smith, Lynne; Miller, Walter L.; Bristow, James.

In: Nature Genetics, Vol. 17, No. 1, 1997, p. 104-108.

Research output: Contribution to journalArticle

Burch, G, Gong, Y, Liu, W, Dettman, RW, Curry, CJ, Smith, L, Miller, WL & Bristow, J 1997, 'Tenascin-X deficiency is associated with Ehlers-Danlos syndrome', Nature Genetics, vol. 17, no. 1, pp. 104-108. https://doi.org/10.1038/ng0997-104
Burch, Grant ; Gong, Yan ; Liu, Wenhui ; Dettman, Robert W. ; Curry, Cynthia J. ; Smith, Lynne ; Miller, Walter L. ; Bristow, James. / Tenascin-X deficiency is associated with Ehlers-Danlos syndrome. In: Nature Genetics. 1997 ; Vol. 17, No. 1. pp. 104-108.
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