Recent progress towards a molecular understanding of Marfan syndrome

被引:154
作者
Dietz, HC
Loeys, B
Carta, L
Ramirez, F
机构
[1] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Inst Med Genet, Baltimore, MD 21205 USA
[2] Cornell Univ, Weill Med Coll, Hosp Special Surg, Div Res, Ithaca, NY 14853 USA
关键词
aortic aneurysm; connective tissue disorder; fibrillin; Marfan syndrome; TGF-beta signaling;
D O I
10.1002/ajmg.c.30068
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Marfan syndrome (MFS) is a systemic disorder of the connective tissue that is inherited as an autosomal dominant trait and which displays variable manifestations in the ocular, skeletal, and cardiovascular systems. These pleiotropic manifestations are accounted for by mutations in fibrillin-1, the building block of extracellular microfibrils. During the past 10 years, we have witnessed significant progress in delineating the pathological events responsible for the manifestations of MFS. Much of this progress has been based on the creation and analysis of fibrillin-1 mutant mouse lines that faithfully recapitulate the spectrum of clinical severity of MFS. These studies have established the critical contribution of fibrillin-1 deficiency to disease progression through altered cell-matrix interactions and dysregulated TGF-beta signaling. As a result, our definition of MFS as the prototypical structural disorder of the connective tissue has changed to that of a developmental abnormality with broad and complex effects on the morphogenesis and function of multiple organ systems. Importantly, new biological targets have emerged that may yield exciting new opportunities for the development of productive treatment strategies in MFS. (c) 2005 Wiley-Liss, Inc.
引用
收藏
页码:4 / 9
页数:6
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