Marfan syndrome: new clues to genotype-phenotype correlations.
Fibrillin 1 is the main constituent of extracellular microfibrils. Microfibrils can exist as individual structures or associate with elastin to form elastic fibres. Fibrillin 1 mutations are the cause of the pleiotropic manifestations of the Marfan syndrome (MFS) which principally involve the musculoskeletal, ocular and cardiovascular systems. MFS pathogenesis requires high levels of mutant fibrillin 1 molecules with dominant-negative activity on microfibrillar assembly and function. Gene-targeting experiments in the mouse have shed new light on fibrillin 1 function, genotype-phenotype correlations and aneurysm progression. These experiments have documented the involvement of fibrillin 1 in maintaining tissue homeostasis, suggested the existence of a critical threshold of functional microfibrils for tissue biomechanics, and outlined novel contributors to the pathogenic sequence of vascular wall collapse.
Ramirez
F
F
Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029, USA. ramirf01@doc.mssm.edu
Gayraud
B
B
Pereira
L
L
D000818:Animals; D004548:Elasticity; D005109:Extracellular Matrix / Q000737:chemistry; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D000071838:Fibrillin-1; D000071837:Fibrillins; D006706:Homeostasis; D006801:Humans; D008382:Marfan Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D009154:Mutation; D054392:Adipokines
D016326:Extracellular Matrix Proteins; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse