BACKGROUND: Mutations in the FBN1 gene are the cause of the Marfan syndrome, an 
autosomal dominant disorder with skeletal, ocular, and cardiovascular 
complications. Aneurysms or dissections of the ascending thoracic aorta are the 
major cardiovascular complications of the disorder. We tested the hypothesis 
that FBN1 mutations cause thoracic aortic aneurysms or dissections in patients 
who do not have the Marfan syndrome.
METHODS AND RESULTS: The FBN1 gene was screened for mutations by use of genomic 
DNA from two patients with thoracic aortic aneurysms who did not have the Marfan 
syndrome. Individual FBN1 exons were amplified with intron-based exon-specific 
primers; the DNA fragments were screened for mutations using single-stranded 
conformational polymorphism analysis; and aberrantly migrating bands were 
sequenced directly. We identified a missense mutation in one patient, D1155N in 
exon 27. Dermal fibroblasts from the affected individual were used to study the 
effect of the missense mutation D1155N on fibrillin-1 cellular processing. The 
mutation decreased the amount of fibrillin-1 deposited into the pericellular 
matrix. A second putative FBN1 mutation was identified in the second patient, 
P1837S in exon 44. Although this alteration was not observed in 234 chromosomes 
from unrelated individuals, the alteration may represent a rare polymorphism.
CONCLUSIONS: Results of these studies support the hypothesis that FBN1 mutations 
cause thoracic aortic aneurysms in patients who do not have the Marfan syndrome. 
This information is important for understanding the pathogenesis of aortic 
aneurysms and identification of individuals at risk for developing thoracic 
aortic aneurysms or dissections.