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

• Published in: The New England journal of medicine Vol. 345; no. 16; pp. 1167 - 1175
• Main Authors: Schalkwijk, Joost, Zweers, Manon C, Steijlen, Peter M, Dean, Willow B, Taylor, Glen, van Vlijmen, Ivonne M, van Haren, Brigitte, Miller, Walter L, Bristow, James
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 18.10.2001
• Subjects: Arthritis, Rheumatoid - blood; Biological and medical sciences; Collagen; DNA Mutational Analysis; Ehlers-Danlos Syndrome - blood; Ehlers-Danlos Syndrome - genetics; Ehlers-Danlos Syndrome - pathology; Enzymes; Female; Gene Deletion; Genes, Recessive; Humans; Male; Medical sciences; Patients; Pedigree; Point Mutation; Proteins; Psoriasis - blood; Reference Values; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin - pathology; Tenascin - blood; Tenascin - deficiency; Tenascin - genetics; tenascin-X; Wound healing; Human; Immunohistochemistry; Tenascin; Skin disease; Elastic tissue disease; Deficiency; Diseases of the osteoarticular system; Clinical form; Genetic disease; Pathology; Gene; Collagen; Ehlers Danlos syndrome; Systemic disease; Genetics; Extracellular matrix; Serum; Skin; Diagnosis; Mutation; Molecular biology; ELISA assay
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa002939

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 ( . . .