Fibrillln mutations in Marfan syndrome and related phenotypes.
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 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 microfibrillin. 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 fibrillin; and the association of fibrillin 2 mutations with congenital contractural arachnodactyly.
Ramirez
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Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029, USA. ramirez@mavax.mssm.edu
D000818:Animals; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D006801:Humans; D008382:Marfan Syndrome / Q000235:genetics* / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D054392:Adipokines
D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605723:FBN2 protein, human