Determination of the molecular basis of Marfan syndrome: a growth industry.
Although it has been known for more than a decade that Marfan syndrome - a dominantly inherited connective tissue disorder characterized by tall stature, arachnodactyly, lens subluxation, and a high risk of aortic aneurysm and dissection - results from mutations in the FBN1 gene, which encodes fibrillin-1, the precise mechanism by which the pleiotropic phenotype is produced has been unclear. A report in this issue now proposes that loss of fibrillin-1 protein by any of several mechanisms and the subsequent effect on the pool of TGF-beta may be more relevant in the development of Marfan syndrome than mechanisms previously proposed in a dominant-negative disease model. The model proposed in this issue demonstrates several strategies for clinical intervention.
Byers
Peter H
PH
Department of Pathology, University of Washington, Seattle, Washington 98195-7470, USA. pbyers@u.washington.edu
D000818:Animals; D002884:Chromosomes, Human, Pair 15; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D008382:Marfan Syndrome / Q000235:genetics / Q000378:metabolism*; D020894:Microfibrils / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D054392:Adipokines
D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D020033:Protein Isoforms; D016212:Transforming Growth Factor beta; C000605722:FBN1 protein, human; D054392:Adipokines