NOTCH3 and CADASIL: Our hypotheses are supported by a growing body of evidence showing that (1) NOTCH3 common variants (rs1043994, rs10404382, rs10423702, and rs1043997) are significantly associated with white matter lesions in elderly with hypertension (Schmidt et al., 2011) and (2) rare noncysteine mutations may be pathogenic as they have been reported in Korean and Japanese CADASIL patients, in a French case with small vessel disease, and have been associated to severe white matter lesions in elderly patients (Fouillade et al., 2008, Mizuno et al., 2008, Schmidt et al., 2011).