Marfan syndrome: new clues to genotype-phenotype correlations

Ann Med. 1999 Jun;31(3):202-7. doi: 10.3109/07853899909115979.


Fibrillin 1 is the main constituent of extracellular microfibrils. Microfibrils can exist as individual structures or associate with elastin to form elastic fibres. Fibrillin 1 mutations are the cause of the pleiotropic manifestations of the Marfan syndrome (MFS) which principally involve the musculoskeletal, ocular and cardiovascular systems. MFS pathogenesis requires high levels of mutant fibrillin 1 molecules with dominant-negative activity on microfibrillar assembly and function. Gene-targeting experiments in the mouse have shed new light on fibrillin 1 function, genotype-phenotype correlations and aneurysm progression. These experiments have documented the involvement of fibrillin 1 in maintaining tissue homeostasis, suggested the existence of a critical threshold of functional microfibrils for tissue biomechanics, and outlined novel contributors to the pathogenic sequence of vascular wall collapse.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Elasticity
  • Extracellular Matrix / chemistry
  • Extracellular Matrix Proteins / chemistry
  • Extracellular Matrix Proteins / deficiency
  • Extracellular Matrix Proteins / genetics*
  • Extracellular Matrix Proteins / physiology
  • Fibrillin-1
  • Fibrillins
  • Homeostasis
  • Humans
  • Marfan Syndrome / genetics*
  • Marfan Syndrome / pathology
  • Marfan Syndrome / physiopathology
  • Mice
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / deficiency
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / physiology
  • Mutation


  • Extracellular Matrix Proteins
  • FBN1 protein, human
  • Fbn1 protein, mouse
  • Fibrillin-1
  • Fibrillins
  • Microfilament Proteins