Abstract
A casual association has been established between mutations in the fibrillin 1 gene and Marfan syndrome and related phenotypes. Analysis of mutations in these disease types has provided new insights into microfibril assembly and function. These include evidence for a mutation in a fibrillin 1 domain associated with the severe phenotype; indication of profibrillin processing by a furin-like endoprotease; linkage between extracellular processing and fibrillin 1 polymerization; and involvement of calcium binding in monomer stabilization and microfibril assembly. Identification of intragenic DNA polymorphisms and determination of intron/exon junction sequences have significantly improved our ability to diagnose Marfan syndrome and to detect fibrillin 1 mutations. Additional work has provided strong evidence for structural and functional heterogeneity of microfibrils. The evidence includes the identification of fibrillin 2, a microfibrillar component structurally related to fibrillin 1; the differential pattern of gene expression of the two fibrillins; and the association of fibrillin 2 mutations with congenital contractural arachnodactyly.
Original language | English |
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Pages (from-to) | 309-315 |
Number of pages | 7 |
Journal | Current Opinion in Genetics and Development |
Volume | 6 |
Issue number | 3 |
DOIs | |
State | Published - Jun 1996 |