Abstract
BACKGROUND: Approximately 10% of patients who undergo surgery for aortic valve disease (stenosis
or regurgitation) suffer from ascending aortic dilation (AAD). A possible genetic
etiology of AAD associated with aortic valve disease has been repeatedly mentioned
in the literature, but a specific responsible gene mutation has not been described.
METHODS: In the present study, two groups of patients were compared, all of whom underwent
surgery for aortic valve disease. Group A was a cohort of 27 patients who suffered
from aortic valve disease associated with AAD. Group B was a cohort of 29 patients
with structural aortic valve disease, but without concomitant AAD (control group).
Genomic DNA was extracted from the white blood cells of peripheral blood samples and
was amplified using primers specific for chosen exons of the fibrillin-1 gene, including
their intron/exon boundaries. Exons 26 and 27 were selected for analysis.
RESULTS: Analysis of the intronic part situated close to exon 27 showed insertion of cytosine
between nucleotide 37 682 and 37 683 of query sequence. This insertions was classified
as IVS 37 682 and 37 683insC. This mutation was found in all 27 patients from group
A (patients with structural aortic valve disease accompanied by significant AAD).
The abovementioned mutation was not found in any of the 29 patients from group B.
CONCLUSIONS: This finding has potential implications for risk stratification and therapeutic targeting
not only for patients with existing disease, but also for the general population.
Future studies are needed to determine the clinical utility of the finding; however,
the present hypothesis needs to be verified by further molecular studies.
