Marfan syndrome: from molecular pathogenesis to clinical treatment.
Marfan syndrome is a connective tissue disorder with ocular, musculoskeletal and cardiovascular manifestations that are caused by mutations in fibrillin-1, the major constituent of extracellular microfibrils. Mouse models of Marfan syndrome have revealed that fibrillin-1 mutations perturb local TGFbeta signaling, in addition to impairing tissue integrity. This discovery has led to the identification of a new syndrome with overlapping Marfan syndrome-like manifestations that is caused by mutations in TGFbeta receptor types I and II. It has also prompted the idea that TGFbeta antagonism will be a productive treatment strategy in Marfan syndrome and perhaps in other related disorders. More generally, these studies have established that Marfan syndrome is part of a group of developmental disorders with broad and complex effects on morphogenesis, homeostasis and organ function.
Ramirez
Francesco
F
Child Health Institute of New Jersey, Robert W. Johnson Medical School, 89 French Street, New Brunswick, NJ 08901, USA. ramirefr@umdnj.edu [corrected]
Dietz
Harry C
HC
D000818:Animals; D003238:Connective Tissue / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008382:Marfan Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
D008840:Microfilament Proteins; D016212:Transforming Growth Factor beta