Genetic Insights into Bicuspid Aortic Valve Formation

Table 1

Human gene mutation and phenotype associated with bicuspid aortic valve formation.

Gene affected	Human syndrome	Human cardiac phenotype	Mutation and/or expression in BAV patients	Mouse valve phenotype	Reference
NOTCH1		BAV, calcification, BAV with aortic aneurysm	R1108X, H1505del, T596M, P179H, A1343V, P1390T	Thick valve leaflets, calcification	[21–23]
GATA6		ASD, TOF	Mother of the ASD patient had a BAV	No valve phenotype reported	[26]
FBN1	Marfan syndrome	Mitral valve prolapse, Aortic aneurysm	Reduced expression of FBN1	Thick and long valve leaflets, mitral valve prolapse	[28–31]
TGFBR2	Loeys-Dielz syndrome, Marfan syndrome	Mitral valve prolapse, aortic aneurysm, BAV	V387M	Defective remodelling of the AV cushion, lethality at E11.5 precluding analysis of valves	[36]
ACTA2		Thoracic aortic aneurysm and dissection	Three family members had a BAV	No valve phenotype	[38]
HOXA1	Bosley-Salih-Alorainy syndrome, athabascan brainstem dysgenesis syndrome	Interrupted aortic arch type B, aberrant subclavian artery, VSD, TOF, BAV	Not reported	BAV	[39]
KCNJ2	Andersen syndrome	BAV, BAV with coarctation of the aorta, pulmonary stenosis	R67W	Not reported	[41]

ASD: atrial septal defect; BAV: bicuspid aortic valve; OFT: outflow tract; TOF: tetralogy of Fallot; VSD: ventricular septal defect.