FROM FLUORESCENCE TO THE GENE - THE SKIN IN THE MARFAN-SYNDROME

[摘要] The Marfan syndrome (MFS) is a heritable connective tissue disorder manifested by defects in the skeletal, ocular, and cardiovascular systems. It is inherited as an autosomal dominant trait, with an incidence of nearly one per 10,000 population without gender or ethnic predilection. About 30% of MFS cases are sporadic, representing new dominant mutations. Although diagnostic criteria may be met, intra- and inter-familial variability in syndromic expression can be quite marked. Life expectancy is significantly reduced, and more than 85% of patients die of cardiovascular complications. Elastin-associated microfibrils are classically identified by a 10-12 nm cross-sectional diameter and close association with amorphous elastin. Characteristically, these microfibrils are seen as a fringe surrounding elastin cores. Despite their name, these fibrils are frequently localized in tissues not associated with elastin. One of the major and best characterized microfibrillar proteins is the glycoprotein, fibrillin. Fibrillin is rich in cysteine residues and thus, extensively intrachain disulfide bonded. Defects in fibrillin are now known to cause the variable and pleiotropic manifestations of MFS. Immunofluorescence studies of skin sections and dermal fibroblast cultures were the first to show this association. The cloning and sequencing of the entire fibrillin coding region has enabled the identification of the myriad of mutations that cause MFS. Identification of the molecular lesions covering the gamut of MFS clinical variability should allow the construction of genotype/phenotype correlations. It is hoped that once available, they may become of prognostic value in the clinical management of MFS.

[发布日期] 1994-11-01

[效力级别]  Proceedings Paper

[关键词] FIBRILLIN;HERITABLE CONNECTIVE TISSUE DISORDERS;FIBROBLASTS;MUTATIONS