The Marfan syndrome is an autosomal dominant connective tissue disorder with 
pleiotropic manifestations affecting skeletal, ocular and cardiovascular 
systems. Because the fibrillar collagens are major structural components of 
connective tissue, the hypothesis has long been set forth that the Marfan 
syndrome is a disorder of fibrillar collagen. We have investigated this 
hypothesis by performing linkage studies in 12 multiplex families with the 
Marfan syndrome, using restriction fragment length polymorphisms (RFLP's) 
associated with 3 genes encoding chains of fibrillar collagens. The data exclude 
linkage to all 3 candidate genes in 2 families and at least 1 of the candidates 
is excluded in 6 additional families. Each candidate was excluded in at least 3 
families. In no case was strong evidence in favor of linkage of the Marfan 
syndrome to any of the 3 genes observed. These data speak against the hypothesis 
that mutations in one or more of these 3 fibrillar collagens cause the classic 
Marfan syndrome.