Fibrillln mutations in Marfan syndrome and related phenotypes

Ramirez, F.

Current Opinion in Genetics and Development 6(3): 309-315


ISSN/ISBN: 0959-437X
PMID: 8791520
DOI: 10.1016/s0959-437x(96)80007-4
Accession: 031442549

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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.