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The molecular pathogenesis of the Marfan syndrome
1Institute of Medical Genetics, Department of General Pediatrics, Charité University Hospital, Berlin, Germany. peter.robinson@charite.de
Abstract:
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.
Insights
Marfan syndrome (MFS) is a heritable connective tissue disorder caused by fibrillin-1 gene mutations. This review covers MFS clinical features and explores current understanding of its pathogenesis.
Area of Science:
- Genetics
- Pathology
- Biochemistry
Background:
- Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder.
- It presents with variable clinical manifestations, including aortic issues, eye problems, and skeletal anomalies.
- Mutations in the fibrillin-1 (FBN1) gene cause MFS and related type-1 fibrillinopathies.
Purpose of the Study:
- To provide an overview of the clinical aspects of Marfan syndrome.
- To discuss current understanding of the pathogenesis of Marfan syndrome.
Main Methods:
- Literature review of clinical and genetic studies on Marfan syndrome.
- Synthesis of current research on fibrillin-1 gene mutations and their impact on connective tissue.
Main Results:
- Fibrillin-1 is crucial for extracellular microfibrils, impacting elastogenesis and tissue homeostasis.
- FBN1 mutations are the primary cause of MFS.
- Pathogenesis theories include dominant negative effects and roles for proteases and tissue homeostasis disruption.
Conclusions:
- Marfan syndrome is a complex disorder with diverse clinical outcomes.
- Understanding fibrillin-1's role is key to elucidating MFS pathogenesis.
- Further research into protease activity and tissue homeostasis may reveal new therapeutic targets.