WHAT GENES ARE RELATED TO CADASIL?
Mutations in the NOTCH3 gene cause CADASIL. The NOTCH3 gene makes a protein called the Notch3 receptor protein, which plays a role in the development, function and maintenance of vascular smooth muscle cells. Mutations in the NOTCH3 gene lead to an abnormal version of the Notch3 protein that builds up in vascular smooth muscle cells. Accumulation of the abnormal Notch3 protein is thought to cause the degeneration of these muscle cells, leading to the loss of function of blood vessels in the brain and heart. WHAT MUTATIONS ARE EFFECTED WITH CADASIL? Almost all CADASIL mutations alter the number of cysteine residues in the epidermal growth factor (EGF)-like repeats in the extra cellular domain of the protein. More than 100 mutations that cause CADASIL have been reported. Almost all of these mutations change a single amino acid (a building block of proteins) in the Notch3 receptor. Evidence suggests that these mutations play a role in the degeneration of vascular smooth muscle cells. Loss
