The molecular pathogenesis of the Marfan syndrome.
The Marfan syndrome (MFS) is an autosomal dominant heritable disorder of connective tissue with highly variable clinical manifestations including aortic dilatation and dissection, ectopia lentis, and a range of skeletal anomalies. Mutations in the gene for fibrillin-1 (FBN1) cause MFS and other related disorders of connective tissue collectively termed type-1 fibrillinopathies. Fibrillin-1 is a main component of the 10- to 12-nm extracellular microfibrils that are important for elastogenesis, elasticity, and homeostasis of elastic fibers. Mutations in fibrillin-1 are hypothesized to exert their effects by dominant negative mechanisms, but recent work has also emphasized the potential role of proteases and disturbances in tissue homeostasis in the pathogenesis of the MFS. This article provides an overview of the clinical aspects of the MFS and current thinking on the pathogenesis of this disorder.
Robinson
P N
PN
Institute of Medical Genetics, Department of General Pediatrics, Charité University Hospital, Berlin, Germany. peter.robinson@charite.de
Booms
P
P
D000818:Animals; D004195:Disease Models, Animal; D004547:Elastic Tissue / Q000502:physiology; D000071838:Fibrillin-1; D000071837:Fibrillins; D006706:Homeostasis; D006801:Humans; D008382:Marfan Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D020894:Microfibrils / Q000378:metabolism / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D010446:Peptide Fragments / Q000378:metabolism; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D054392:Adipokines
D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C000605722:FBN1 protein, human; D054392:Adipokines