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Previous Volume 345:1167-1175 October 18, 2001 Number 16 Next

	Full Text PDF Editorial by Byers, P. H. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background The Ehlers–Danlos syndrome is a heritable connective-tissue disorder caused by defects in fibrillar-collagen metabolism. Mutations in the type V collagen genes account for up to 50 percent of cases of classic Ehlers–Danlos syndrome, but many other cases are unexplained. We investigated whether the deficiency of the tenascins, extracellular-matrix proteins that are highly expressed in connective tissues, was associated with the Ehlers–Danlos syndrome.

Methods We screened serum samples from 151 patients with the classic, hypermobility, or vascular types of the Ehlers–Danlos syndrome; 75 patients with psoriasis; 93 patients with rheumatoid arthritis; and 21 healthy persons for the presence of tenascin-X and tenascin-C by enzyme-linked immunosorbent assay. We examined the expression of tenascins and type V collagen in skin by immunohistochemical methods and sequenced the tenascin-X gene.

Results Tenascin-X was present in serum from all normal subjects, all patients with psoriasis, all patients with rheumatoid arthritis, and 146 of 151 patients with the Ehlers–Danlos syndrome. Tenascin-X was absent from the serum of the five remaining patients with Ehlers–Danlos syndrome, who were unrelated. Tenascin-X deficiency was confirmed in these patients by analysis of skin fibroblasts and by immunostaining of skin. The expression of tenascin-C and type V collagen was normal in these patients. All five of these patients had hypermobile joints, hyperelastic skin, and easy bruising, without atrophic scarring. Tenascin-X mutations were identified in all tenascin-X–deficient patients; one patient had a homozygous tenascin-X gene deletion, one was heterozygous for the deletion, and three others had homozygous truncating point mutations, confirming a causative role for tenascin-X and a recessive pattern of inheritance.

Conclusions Tenascin-X deficiency causes a clinically distinct, recessive form of the Ehlers–Danlos syndrome. This finding indicates that factors other than the collagens or collagen-processing enzymes can cause the syndrome and suggests a central role for tenascin-X in maintaining the integrity of collagenous matrix.

Source Information

From the Department of Dermatology, University Medical Center Nijmegen, Nijmegen, the Netherlands (J.S., M.C.Z., P.M.S., I.M.V., B.H.); and the Department of Pediatrics, University of California at San Francisco, San Francisco (W.B.D., G.T., W.L.M., J.B.).

Address reprint requests to Dr. Bristow at the University of California at San Francisco, Laurel Heights Campus, 3333 California St., Box 1245, San Francisco, CA 94118, or at jbristow{at}pedcard.ucsf.edu, or to Dr. Schalkwijk at the Department of Dermatology, UMCN, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands, or at j.schalkwijk{at}derma.azn.nl

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