Fibrillln mutations in Marfan syndrome and related phenotypes

Curr Opin Genet Dev. 1996 Jun;6(3):309-15. doi: 10.1016/s0959-437x(96)80007-4.

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 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Fibrillin-1
  • Fibrillin-2
  • Fibrillins
  • Humans
  • Marfan Syndrome / genetics*
  • Marfan Syndrome / metabolism
  • Microfilament Proteins / genetics*
  • Muscle Fibers, Skeletal / metabolism
  • Mutation
  • Phenotype

Substances

  • FBN1 protein, human
  • FBN2 protein, human
  • Fibrillin-1
  • Fibrillin-2
  • Fibrillins
  • Microfilament Proteins