Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, a dominantly 
inherited disorder of connective tissue that primarily involves the 
cardiovascular, ocular, and skeletal systems. There is a remarkable degree of 
variability both within and between families with Marfan syndrome, and FBN1 
mutations have also been found in a range of other related connective tissue 
disorders collectively termed type-1 fibrillinopathies. FBN1 mutations have been 
found in almost all of the 65 exons of the FBN1 gene and for the most part have 
been unique to one affected patient or family. Aside from the "hot spots" for 
the neonatal Marfan syndrome in exons 24-27 and 31-32, genotype-phenotype 
correlations have been slow to emerge. Here we present the results of 
temperature-gradient gel electrophoresis analysis of FBN1 exons 59-65. Six 
mutations were identified, only one of which had been previously reported. Two 
of the six mutations were found in patients with mild phenotypes. Taken together 
with other published reports, our results suggest that a sizable subset (ca. 
40%) of mutations in this region is associated with mild phenotypes 
characterized by the lack of significant aortic pathology, compared with about 
7% in the rest of the gene. In two cases, mutations affecting analogous 
positions within one of the 43 cbEGF modules of FBN1 are associated with mild 
phenotypes when found in one of the 6 C-terminal modules (encoded by exons 
59-63), but are associated with classic or severe phenotypes when found in cbEGF 
modules elsewhere in the gene.