Our study here identified G73A as a new mutation in NOTCH3 to cause CADASIL and revealed that the G73A mutation and two known mutants R75P and R133C decreased NOTCH3 protein turnover and induced cell death.
We diagnosed CADASIL after detecting granular osmiophilic material in the walls of the endoneurial vessels morphologically and identifying a heterozygous NOTCH3 mutation p.Arg75Pro.
The novel mutation of R75P, not involving a cysteine residue, is related to less frequent involvement of the anterior temporal area, thus broadening the spectrum of CADASIL.