Published online by Cambridge University Press: 09 November 2011
In our recent study, we first reported that mutation in vascular endothelial growth factor-A is associated with bicuspid aortic valve stenosis. However, to date no groups have explored the role of vascular endothelial growth factor-A variations in the aetiology of congenital tricuspid aortic valve stenosis.
We sequenced all eight coding exons and exon–intron boundaries of the vascular endothelial growth factor-A gene in deoxyribonucleic acid samples of a cohort of 32 sporadic patients with tricuspid aortic valve stenosis, 300 normal controls, and 103 disease controls – conotruncal defects – in order to identify sequence variants.
We identified a c.973C > T heterozygous nonsense variation in exon 6 of the vascular endothelial growth factor-A gene in a patient with an isolated tricuspid aortic valve stenosis. The c.973C > T variation, which was absent in all controls, changes a highly conserved arginine at amino acid position 325 to a stop codon (p.Arg325X) and is predicted to produce a truncated protein of 324 amino acid residues. The proband's parents had a normal cardiac phenotype; however, his father was a carrier of the p.Arg325X variation, which indicates that the p.Arg325X variation is inherited and incompletely penetrant.
We report for the first time that the p.Arg325X nonsense variation in the vascular endothelial growth factor-A gene may be associated with congenital tricuspid aortic valve stenosis.