NOTCH1-related Tetralogy of Fallot

NOTCH1-related Tetralogy of Fallot is a conotruncal heart malformation defined by ventricular septal defect, overriding aorta, right-ventricular outflow obstruction and secondary right-ventricular hypertrophy. Severity depends mainly on the degree of outflow obstruction and associated cardiovascular anomalies.
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Genetics

Tetralogy of Fallot is genetically heterogeneous; this centre project is NOTCH1-related. Heterozygous loss-of-function and damaging missense NOTCH1 variants show variable penetrance and can also cause other left- or right-sided congenital heart defects.

Molecular Mechanism

NOTCH1 signaling controls cardiac progenitor differentiation, endocardial-cushion formation, neural-crest contributions and outflow-tract septation. Reduced or mis-timed signaling can misalign the outlet septum and disturb semilunar-valve and ventricular development.

Therapy

Clinical treatment is surgical repair followed by lifelong congenital-cardiology surveillance for residual obstruction, pulmonary regurgitation, right-ventricular dysfunction and arrhythmia. There is no molecular therapy for established anatomy.

CCP Activity

CCP is developing an inducible NOTCH1-related model to study embryonic outflow-tract morphogenesis in collaboration with professor David Sedmera from First Medical Faculty, Charles University. Functional high resolution prenatal and perinatal echocardiography will be used for characterization of neonatal cardiac dynamic.

Mouse Models Mouse Models & Gene Cards

Mouse ModelsGene Cards
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