Overlapping but distinct roles for NOTCH receptors in human cardiovascular disease

• Published in: Clinical genetics Vol. 95; no. 1; pp. 85 - 94
• Main Authors: Meester, J.A.N., Verstraeten, A., Alaerts, M., Schepers, D., Van Laer, L., Loeys, B.L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2019
• Subjects: Adams‐Oliver syndrome; Alagille syndrome; Alagille Syndrome - genetics; Alagille Syndrome - pathology; Aortic valve; bicuspid aortic valve; CADASIL; CADASIL - genetics; CADASIL - pathology; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - genetics; Cardiovascular Diseases - pathology; Cell death; Cell fate; Cell proliferation; Cell Proliferation - genetics; Congenital diseases; congenital heart defects; Coronary artery disease; Ectodermal Dysplasia - genetics; Ectodermal Dysplasia - pathology; Heart diseases; Humans; Leukoencephalopathy; Limb Deformities, Congenital - genetics; Limb Deformities, Congenital - pathology; Mutation; NOTCH receptor; Notch1 protein; Notch2 protein; Notch3 protein; Notch4 protein; Phenotypes; Receptor, Notch1 - genetics; Receptor, Notch2 - genetics; Receptor, Notch3 - genetics; Rheumatic heart disease; Scalp Dermatoses - congenital; Scalp Dermatoses - genetics; Scalp Dermatoses - pathology; Signal transduction; mutation; CADASIL; Adams-Oliver syndrome; Alagille syndrome; bicuspid aortic valve; NOTCH receptor; cardiovascular diseases; congenital heart defects
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.13382

The NOTCH signalling pathway is an essential pathway, involved in many cellular processes, including cell fate decision, cell proliferation, and cell death and important in the development of most organs. Mutations in genes encoding components of the NOTCH signalling pathway lead to a spectrum of congenital disorders. Over the past decades, mutations in human NOTCH signalling genes have been identified in several diseases with cardiovascular involvement. NOTCH1 mutations have been described in bicuspid aortic valve disease, left‐sided congenital heart disease, and Adams‐Oliver syndrome. NOTCH2 mutations lead to the development of Alagille syndrome, while mutations in NOTCH3 cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. To date, mutations in NOTCH4 have not been associated with cardiovascular disease. This review focuses on the mutations described in NOTCH1, NOTCH2, and NOTCH3 and their associated cardiovascular phenotypes.