The molecular genetics of Marfan syndrome and related disorders.
Résumé
Marfan syndrome (MFS), a relatively common autosomal dominant hereditary disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular systems, is caused by mutations in the gene for fibrillin-1 (FBN1). The leading cause of premature death in untreated individuals with MFS is acute aortic dissection, which often follows a period of progressive dilatation of the ascending aorta. Recent research on the molecular physiology of fibrillin and the pathophysiology of MFS and related disorders has changed our understanding of this disorder by demonstrating changes in growth factor signalling and in matrix-cell interactions. The purpose of this review is to provide a comprehensive overview of recent advances in the molecular biology of fibrillin and fibrillin-rich microfibrils. Mutations in FBN1 and other genes found in MFS and related disorders will be discussed, and novel concepts concerning the complex and multiple mechanisms of the pathogenesis of MFS will be explained.
Mots clés
Topics: 11
259 Abbreviations: BMP
bone morphogenetic protein
cbEGF
calcium binding epidermal growth factor
CCA
congenital contractural arachnodactyly
CMN
cystic medial necrosis
CSGE
conformation sensitive gel electrophoresis
DHPLC
denaturing high performance liquid chromatography
EBP
elastin-binding protein
ECM
extracellular matrix
HNPCC
hereditary non- polyposis colorectal cancer
LAP
latency-associated peptide
LDS
Loeys-Dietz aortic aneurysm syndrome
LLC
large latent complexes
LTBPs
latent-TGFb-binding proteins
MAGP-1
microfibril-associated glycoprotein-1
MFS
Marfan syndrome
MFS2
type 2 Marfan syndrome
MMP
matrix metalloproteinase
MMR
mismatch repair
MSI
microsatellite instability
NMR
nuclear magnetic resonance
PTC
premature termination codon
SSCP
single stranded conformation polymorphism
TAAD
thoracic ascending aortic aneurysms and dissections
TbRII
type II TGFb receptor
TGFb
transforming growth factor-b
UMD
Universal Mutation Database
WMS
Weill-Marchesani syndrome 1
Domaines
GénétiqueOrigine | Fichiers produits par l'(les) auteur(s) |
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