FIBRILLIN SECRETION AND MICROFIBRIL ASSEMBLY BY MARFAN DERMAL FIBROBLASTS

The Marfan syndrome has been linked to the FBN1 gene encoding the micr ofibrillar glycoprotein fibrillin. To date, there have been no descrip tions of microfibrillar abnormalities characteristic of this connectiv e tissue disorder, although biochemical analyses have highlighted appa rent abnormalities in fibrillin synthesis, secretion and processing. W e have conducted a biochemical and ultrastructural investigation of fi brillin expression and assembly by a panel of dermal fibroblast lines from patients with Marfan syndrome and related diseases. The study has highlighted marked differences between cells in terms of secretion an d aggregation of newly-synthesised fibrillin. In addition, electron mi croscopic visualization of fibrillin assemblies has clearly demonstrat ed for the first time the plethora of microfibrillar abnormalities tha t underlie this heterogeneous disorder. These data emphasize the molec ular complexity that is a feature of the diverse clinical phenotypes e xhibited by Marfan patients.