A novel SMAD6 variant in a patient with severely calcified bicuspid aortic valve and thoracic aortic aneurysm
- Title
- A novel SMAD6 variant in a patient with severely calcified bicuspid aortic valve and thoracic aortic aneurysm
- Author
- 박종은
- Keywords
- bicuspid aortic valve; SMAD6; whole exome sequencing
- Issue Date
- 2019-05
- Publisher
- WILEY
- Citation
- MOLECULAR GENETICS & GENOMIC MEDICINE, v. 7, no. 5, article no. e620
- Abstract
- Background: Bicuspid aortic valve (BAV) is the most common congenital heart defect with a prevalence of 1%-2% in the general population. NOTCH1, SMAD6, and GATA5 are associated with BAV in humans, but few cases have been reported that did not involve NOTCH1. Here, we identified novel in-frame variants in SMAD6 (c.1168_1173dup; p.Gly390_Ile391dup) in a BAV patient, who presented with dilatation of the ascending aorta and severe calcification of the aortic valve.
Methods: Twenty BAV associated genes were screened by exome sequencing. Functional effects of SMAD6 variant were investigated using bone morphogenetic protein (BMP) signaling assays through in vitro functional study.
Results: Exome sequencing revealed he had novel in-frame variants in the SMAD6 gene (c.1168_1173dup; p.Gly390_Ile391dup). SMAD6 is known to be an inhibitory protein in the BMP signaling pathway. In vitro functional study of the p.Gly390_Ile391dup variant revealed impaired inhibition of BMP signaling and BMP-induced alkaline phosphatase activity.
Conclusion: In conclusion, we identified a novel SMAD6 variant causing a severely calcified BAV and TAA, which contributes to our understanding of the clinical and genetic background of SMAD6-related BAV.
- URI
- https://onlinelibrary.wiley.com/doi/full/10.1002/mgg3.620https://repository.hanyang.ac.kr/handle/20.500.11754/161910
- ISSN
- 2324-9269
- DOI
- 10.1002/mgg3.620
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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