Mutations in fibrillin-1 cause congenital scleroderma: stiff skin syndrome.
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ABSTRACT:
SUBMITTER: Loeys BL
PROVIDER: S-EPMC2953713 | biostudies-literature | 2010 Mar
REPOSITORIES: biostudies-literature
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Mutations in fibrillin-1 cause congenital scleroderma: stiff skin syndrome.
Loeys B L BL Gerber E E EE Riegert-Johnson D D Iqbal S S Whiteman P P McConnell V V Chillakuri C R CR Macaya D D Coucke P J PJ De Paepe A A Judge D P DP Wigley F F Davis E C EC Mardon H J HJ Handford P P Keene D R DR Sakai L Y LY Dietz H C HC
Science translational medicine 20100301 23
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 ...[more]
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