Marfan syndrome is an autosomal dominant connective tissue disorder caused by 
mutations in the fibrillin gene FBN1, which encodes an extracellular matrix 
glycoprotein. Major features of Marfan syndrome occur in the ocular, 
cardiovascular, and skeletal systems as well as in the dura mater. Approximately 
60% of known disease-causing mutations are missense mutations of single amino 
acid residues. Effects on the cardiovascular system are classically associated 
with mutations in exons 24-32 of the 65 FBN1 exons and many, though not all, 
reports associate missense mutations in exons 59-65 with a mild cardiovascular 
phenotype. Here we present 5 related individuals among whom a c.7409G>A 
(p.Cys2470Tyr) missense variant in exon 59 of FBN1 is associated with 
significant cardiovascular features. The index case also had an apparently de 
novo 46,XX,del(5)(q33.1q33.3) deletion on chromosome 5. This family demonstrates 
skeletal, dermatological and neurological features consistent with Marfan 
syndrome but lacks significant ophthalmological findings to date. These findings 
suggest that FBN1 C-terminal missense mutations may not confer the 
ophthalmological features of Marfan syndrome, but they also confer a more 
significant risk for cardiovascular pathology than that suggested by previous 
studies. Furthermore, clinical data from this family supports the previously 
reported association of dural ectasia with C-terminal mutations.