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A nonsense variation p.Arg325X in the vascular endothelial growth factor-A gene may be associated with congenital tricuspid aortic valve stenosis

Published online by Cambridge University Press:  09 November 2011

Wu Zhao ,
Jian Wang ,
Jie Shen ,
Kun Sun ,
Yiwei Chen ,
Wei Ji ,
Lijun Fu ,
Yurong Wu  and
Fen Li
Wu Zhao
Affiliation:
Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China Department of Pediatrics, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province, People's Republic of China
Jian Wang
Affiliation:
Research Division of Birth Defects, Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai, People's Republic of China
Jie Shen
Affiliation:
Department of Cardiology, Shanghai Children's Hospital, Shanghai, People's Republic of China
Kun Sun
Affiliation:
Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China
Yiwei Chen
Affiliation:
Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China
Wei Ji
Affiliation:
Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China
Lijun Fu
Affiliation:
Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China
Yurong Wu
Affiliation:
Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China
Fen Li*
Affiliation:
Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China
*
Correspondence to: Dr F. Li, Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, People's Republic of China. Tel: +86 21 38626161; Fax: +86 21 58393915; E-mail: [email protected]
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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

Keywords

Congenital cardiac diseasegeneticssequence analysis
Type
Original Article
Information
Cardiology in the Young , Volume 22 , Issue 3 , June 2012 , pp. 316 - 322
Copyright
Copyright © Cambridge University Press 2012

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