Abstract
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-β 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4-9 |
| Number of pages | 6 |
| Journal | American Journal of Medical Genetics - Seminars in Medical Genetics |
| Volume | 139 C |
| Issue number | 1 |
| DOIs | |
| State | Published - Nov 15 2005 |
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Keywords
- Aortic aneurysm
- Connective tissue disorder
- Fibrillin
- Marfan syndrome
- TGF-β signaling
ASJC Scopus subject areas
- Genetics(clinical)
- Neuropsychology and Physiological Psychology
- Neuroscience(all)
Cite this
Recent progress towards a molecular understanding of Marfan syndrome. / Dietz, Harry C; Loeys, Bart; Carta, Luca; Ramirez, Francesco.
In: American Journal of Medical Genetics - Seminars in Medical Genetics, Vol. 139 C, No. 1, 15.11.2005, p. 4-9.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Recent progress towards a molecular understanding of Marfan syndrome
AU - Dietz, Harry C
AU - Loeys, Bart
AU - Carta, Luca
AU - Ramirez, Francesco
PY - 2005/11/15
Y1 - 2005/11/15
N2 - 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-β 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.
AB - 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-β 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.
KW - Aortic aneurysm
KW - Connective tissue disorder
KW - Fibrillin
KW - Marfan syndrome
KW - TGF-β signaling
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UR - http://www.scopus.com/inward/citedby.url?scp=28444470470&partnerID=8YFLogxK
U2 - 10.1002/ajmg.c.30068
DO - 10.1002/ajmg.c.30068
M3 - Article
C2 - 16273535
AN - SCOPUS:28444470470
VL - 139 C
SP - 4
EP - 9
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 1
ER -