Marfan syndrome: new clues to genotype-phenotype correlations

Fibrillin 1 is the main constituent of extracellular microfibrils. Microfib rils can exist as inividual structures or associate with elastin to form el astic fibres. Fibrillin 1 mutations are the cause of the pleiotropic manife stations of the Marfan syndrome (MFS) which principally involve the musculo skeletal, 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 mou se have shed new light on fibrillin 1 function, genotype-phenotype correlat ions and aneurysm progression. These experiments have documented the involv ement of fibrillin 1 in mantaining tissue homeostasis, suggested the existe nce of a critical threshold of functional microfibrils for tissue biomechan ics, and outlined novel contributors to the pathogenic sequence of vascular wall collapse.