BACKGROUND: Mutations in the fibrillin-1 gene have been identified in patients 
with Marfan syndrome (MFS). This study aimed to identify the molecular defects 
in the fibrillin-1 gene in a Chinese family with Marfan syndrome, accompanied by 
aortic aneurysms/dissection.
METHODS: Two patients and one non-carrier in the family underwent complete 
physical, ophthalmic, and cardiovascular examinations. Genomic DNA was extracted 
from leukocytes of venous blood of these individuals in the family as well as 50 
healthy normal controls. Polymerase chain reaction amplification and direct 
sequencing of all 65 coding exons of fibrillin-1 gene were analyzed.
RESULTS: We found a novel mutation (c.8547T > G, p.Tyr2849X) in exon 65 of 
fibrillin-1 gene in a Chinese proband with Marfan syndrome, accompanied by 
aortic aneurysms/dissection. Sudden death at a young age of affected members was 
seen due to aortic aneurysms/dissection. By evaluating genotype-phenotype 
correlations of patients with mutations in the 3' end of fibrillin-1 gene (exons 
64 and 65), we also found that the presence of nonsense mutations occurring in 
exons 64 and 65 appeared to be an indicator of early-onset aortic risk and 
sudden death.
CONCLUSIONS: These results expand the mutation spectrum of fibrillin-1 gene and 
help in the study of the molecular pathogenesis of Marfan syndrome, indicating 
that mutations occurring in the 3' end of fibrillin-1 gene may play an 
independent functional role in the pathogenesis of Marfan syndrome.