TENASCIN-X DEFICIENCY IS ASSOCIATED WITH EHLERS-DANLOS-SYNDROME

The tenascins are a family of large extracellular matrix proteins with at least three members: tenascin-X (TNX)(1-3), tenascin-C (TNC, or cy totactin)(4-6) and tenascin-R (TN-R, or restrictin)(7,8). Although the tenascins have been implicated in a number of important cellular proc esses, no function has been clearly established for any tenascin(9). W e describe a new contiguous-gene syndrome, involving the CYP21B and TN X genes, that results in 21-hydroxylase deficiency and a connective-ti ssue disorder consisting of skin and joint hyperextensibility, vascula r fragility and poor wound healing. The connective tissue findings are typical of the Ehlers-Danlos syndrome (EDS)(10). The abundant express ion of TNX in connective tissues(2,11-13) 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 ari sing from recombination between TNX and its partial duplicate gene, XA (14), which precludes TNX synthesis. Absence of TNX mRNA and protein i n the proband, mapping of the TNX gene and HLA typing of this family s uggest recessive inheritance of TNX deficiency and connective-tissue d isease. Although the precise role of TNX in the pathogenesis of EDS is uncertain, this patient's findings suggest a unique and essential rol e for TNX in connective-tissue structure and function.