Abstract
Marfan syndrome (MFS), a relatively common autosomal dominant hereditary disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular systems, is caused by mutations in the gene for fibrillin-1 (FBN1). The leading cause of premature death in untreated individuals with MFS is acute aortic dissection, which often follows a period of progressive dilatation of the ascending aorta. Recent research on the molecular physiology of fibrillin and the pathophysiology of MFS and related disorders has changed our understanding of this disorder by demonstrating changes in growth factor signalling and in matrix-cell interactions. The purpose of this review is to provide a comprehensive overview of recent advances in the molecular biology of fibrillin and fibrillin-rich microfibrils. Mutations in FBN1 and other genes found in MFS and related disorders will be discussed, and novel concepts concerning the complex and multiple mechanisms of the pathogenesis of MFS will be explained.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Activin Receptors, Type I / genetics
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Animals
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Aortic Aneurysm, Thoracic / genetics
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Aortic Dissection / genetics
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Contractile Proteins / physiology
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Databases, Genetic
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Extracellular Matrix Proteins / physiology
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Fibrillin-1
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Fibrillins
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Humans
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Latent TGF-beta Binding Proteins / genetics
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Marfan Syndrome / complications
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Marfan Syndrome / genetics*
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Mice
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Microfibrils / metabolism
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Microfilament Proteins / genetics
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Models, Animal
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Models, Biological
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Protein Denaturation / genetics
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Protein Serine-Threonine Kinases
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RNA Splicing Factors
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Receptor, Transforming Growth Factor-beta Type I
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Transforming Growth Factor beta / genetics
Substances
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Contractile Proteins
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Extracellular Matrix Proteins
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FBN1 protein, human
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Fbn1 protein, mouse
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Fibrillin-1
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Fibrillins
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Latent TGF-beta Binding Proteins
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Microfilament Proteins
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RNA Splicing Factors
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Receptors, Transforming Growth Factor beta
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microfibrillar protein
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Protein Serine-Threonine Kinases
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Activin Receptors, Type I
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Receptor, Transforming Growth Factor-beta Type I
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Receptor, Transforming Growth Factor-beta Type II