To further decipher the association of genetic landscape in NOTCH-signaling genes with CAVD, we sequenced coding and non-coding regions of 20 genes involved in the NOTCH-signaling cascade (DVL2, DTX2, MFNG, NUMBL, LFNG, DVL1, DTX4, APH1A, DTX1, APH1B, NOTCH1, ADAM17, DVL3, NCSTN, DTX3L, ILK, RFNG, DTX3, NOTCH4, PSENEN) in a cohort of 90 patients diagnosed with AS. The gene discussed is NOTCH4; the disease is aortic stenosis.