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Mutations in Fibrillin-1 Cause Congenital Scleroderma: Stiff Skin Syndrome
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 sequenceâencoding domain of fibrillin-1 that media...
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Published in: | Science translational medicine 2010-03, Vol.2 (23), p.23ra20-23ra20 |
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Main Authors: | , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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
sequenceâencoding 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 factorâβ
(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. |
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ISSN: | 1946-6234 1946-6242 |
DOI: | 10.1126/scitranslmed.3000488 |