A Recessive Form of the Ehlers–Danlos Syndrome Caused by Tenascin-X Deficiency

Up to half of people with classic Ehlers–Danlos syndrome, a condition marked by hyperextensible skin, hypermobile joints, and tissue fragility, have mutations of the genes for type V collagen, raising the possibility that other genes may also be involved. Because tenascins are extracellular-matrix proteins with high levels of expression in connective tissues affected in the Ehlers–Danlos syndrome, these investigators searched for genetic defects in tenascin-X as a potential cause. Tenascin-X deficiency was found in 5 unrelated patients with the Ehlers–Danlos syndrome (of 151 screened), all of whom had distinct mutations in the tenascin-X gene. The Ehlers–Danlos syndrome is a genetically heterogeneous group of heritable connective-tissue disorders characterized by hyperextensible skin, hypermobile joints, and tissue fragility. 1 , 2 Ultrastructural studies of the skin in the Ehlers–Danlos syndrome frequently reveal abnormal heterotypic collagen fibrils containing collagen types I, III, and V, indicating that the syndrome is a disorder of the collagen fibril. 3 This concept is supported by the identification of mutations in genes encoding the fibrillar collagens or collagen-modifying enzymes in patients with the Ehlers–Danlos syndrome. 4 – 12 Thirty to 50 percent of patients with classic Ehlers–Danlos syndrome have haploinsufficiency of the gene encoding type V collagen ( . . .