Novel variants in PIEZO1 are associated with bicuspid aortic valve (BAV)

The bicuspid aortic valve (BAV) is a congenital defect found in 1-2% of the population and is the most common valve malformation. A bicuspid valve is comprised of two rather than three semilunar leaflets (or cusps). BAV is clinically relevant because most affected patients develop functional valve defects and/or aortopathies during their lifetime. We used whole exome sequencing on a local cohort named BAP (Bicuspid Aortic valve Project conducted in Marseille) to identify 3 independent nonsynonymous variants in PIEZO1. PIEZO1 is a mechanosensitive ion channel present in endothelial cells where it serves to detect hemodynamic forces. By analysing heart development in zebrafish we have determined that piezo1 is expressed in the developing outflow tract where it serves to detect hemodynamic forces.Consequently, disrupting Piezo1 signalling leads to defective outflow tract and aortic valve development and indicates this gene may be involved in the etiology of congenital heart diseases.

 

Faucherre A., et al., Piezo1 is required for outflow tract and aortic valve development. J Mol Cell Cardiol, (2020) doi: 10.1016/j.yjmcc.2020.03.013 (Online ahead of print 03 April 2020)

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