The molecular genetics of Marfan syndrome and related disorders

• Published in: Journal of Medical Genetics 2006-10, Vol.43 (10), p.769-787
• Main Authors: Robinson, P N, Arteaga-Solis, E, Baldock, C, Collod-Béroud, G, Booms, P, De Paepe, A, Dietz, H C, Guo, G, Handford, P A, Judge, D P, Kielty, C M, Loeys, B, Milewicz, D M, Ney, A, Ramirez, F, Reinhardt, D P, Tiedemann, K, Whiteman, P, Godfrey, M
• Format: Article
• Language: English
• Subjects: Activin Receptors, Type I; Activin Receptors, Type I - genetics; Aneurysm, Dissecting; Aneurysm, Dissecting - genetics; Animals; Aortic Aneurysm, Thoracic; Aortic Aneurysm, Thoracic - genetics; Biological and medical sciences; BMP; bone morphogenetic protein; calcium binding epidermal growth factor; cbEGF; CCA; Chemical bonds; CMN; conformation sensitive gel electrophoresis; congenital contractural arachnodactyly; Contractile Proteins; Contractile Proteins - physiology; CSGE; cystic medial necrosis; Databases, Genetic; denaturing high performance liquid chromatography; DHPLC; EBP; ECM; elastin-binding protein; Epidermal growth factor; Extracellular matrix; Extracellular Matrix Proteins; Extracellular Matrix Proteins - physiology; fibrillin; Fibrillin-1; Fibrillins; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genes; Genetics; Genetics of eukaryotes. Biological and molecular evolution; hereditary non-polyposis colorectal cancer; HNPCC; Humans; LAP; large latent complexes; latency-associated peptide; Latent TGF-beta Binding Proteins; Latent TGF-beta Binding Proteins - genetics; latent-TGFβ-binding protein; LDS; Life Sciences; LLC; Loeys-Dietz aortic aneurysm syndrome; LTBP; MAGP-1; Marfan Syndrome; Marfan Syndrome - complications; Marfan Syndrome - genetics; matrix metalloproteinase; Medical genetics; Medical sciences; MFS; MFS2; Mice; microfibril; microfibril-associated glycoprotein-1; Microfibrils; Microfibrils - metabolism; Microfilament Prot; Microfilament Proteins - genetics; microsatellite instability; mismatch repair; MMP; MMR; Models, Animal; Models, Biological; Molecular and cellular biology; MSI; Mutation; NMR; nuclear magnetic resonance; Pathogenesis; premature termination codon; Protein Denaturation - genetics; Protein-Serine-Threonine Kinases; PTC; Receptors, Transforming Growth Factor beta - genetics; Review; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; single stranded conformation polymorphism; SSCP; Studies; TAAD; TGFβ; thoracic ascending aortic aneurysms and dissections; transforming growth factor-β; type 2 Marfan syndrome; type II TGFβ receptor; TβRII; UMD; Universal Mutation Database; Weill-Marchesani syndrome; WMS
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2005.039669

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.