Most previously reported mutations in cerebral autosomal dominant arteriopathy 
with subcortical infarcts and leukoencephalopathy (CADASIL) result in an odd 
number of cysteine residues within the epidermal growth factor (EGF)-like 
repeats in Notch3. We report here R75P mutation in two Japanese CADASIL families 
not directly involving cysteine residues located within the first EGF-like 
repeats. Probands in both families had repeated episodes of stroke, depression, 
dementia as well as T2 high-intensity lesions in the basal ganglia and 
periventricular white matter, but fewer white matter lesions in the temporal 
pole on MRI. These families provide new insights into the diagnosis and 
pathomechanisms of CADASIL.