Mutations in the gene encoding fibrillin-1 (FBN1), a component of the 
extracellular microfibril, cause the Marfan syndrome (MFS). This statement is 
supported by the observations that the classic Marfan phenotype cosegregates 
with intragenic and/or flanking marker alleles in all families tested and that a 
significant number of FBN1 mutations have been identified in affected 
individuals. We have now devised a method to screen the entire coding sequence 
and flanking splice junctions of FBN1. On completion for a panel of nine 
probands with classic MFS, six new mutations were identified that accounted for 
disease in seven (78%) of nine patients. Nine additional new mutations have been 
characterized in the early stages of a larger screening project. These 15 
mutations were equally distributed throughout the gene and, with one exception, 
were specific to single families. One-third of mutations created premature 
termination codons, and 6 of 15 substituted residues with putative significance 
for calcium binding to epidermal growth factor (EGF)-like domains. Mutations 
causing severe and rapidly progressive disease that presents in the neonatal 
period can occur in a larger region of the gene than previously demonstrated, 
and the nature of the mutation is as important a determinant as its location, in 
predisposing to this phenotype.