We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Mutations in Fibrillin-1 Cause Congenital Scleroderma: Stiff Skin Syndrome.
- Authors
Loeys, B. L.; Gerber, E. E.; Riegert-Johnson, D.; Iqbal, S.; Whiteman, P.; McConnell, V.; Chillakuri, C. R.; Macaya, D.; Coucke, P. J.; De Paepe, A.; Judge, D. P.; Wigley, F.; Davis, E. C.; Mardon, H. J.; Handford, P.; Keene, D. R.; Sakai, L. Y.; Dietz, H. C.
- Abstract
The predisposition for scleroderma, defined as fibrosis and hardening of the skin, is poorly understood. We report that stiff skin syndrome (SSS), an autosomal dominant congenital form of scleroderma, is caused by mutations in the sole Arg-Gly-Asp sequence-encoding domain of fibrillin-1 that mediates integrin binding. Ordered polymers of fibrillin-1 (termed microfibrils) initiate elastic fiber assembly and bind to and regulate the activation of the profibrotic cytokine transforming growth factor-β (TGFβ). Altered cell-matrix interactions in SSS accompany excessive microfibrillar deposition, impaired elastogenesis, and increased TGFβ concentration and signaling in the dermis. The observation of similar findings in systemic sclerosis, a more common acquired form of scleroderma, suggests broad pathogenic relevance.
- Publication
Science Translational Medicine, 2010, Vol 2, Issue 23, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.3000488