Some missense mutations and small deletions in the NOTCH3 gene, not involving 
cysteine residues, have been described in patients considered to be affected by 
paucisymptomatic CADASIL. However, the significance of such molecular variants 
is still unclear. We describe a 49-year-old woman with a CADASIL-like phenotype, 
carrying a novel cysteine-sparing mutation in exon 29 of the NOTCH3 gene, and 
discuss the possible pathogenetic role of this molecular variant. Even though 
atypical clinical and MRI findings make a diagnosis of CADASIL unlikely in this 
patient, our report nevertheless underlines the intriguing genotype-phenotype 
relationship in NOTCH3 mutations and the importance of functional investigation 
to ascertain the role of new NOTCH3 mutations in CADASIL pathogenesis.