A novel cysteine-sparing NOTCH3 mutation in a Chinese family with CADASIL.

[cadasil]

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL ) is an adult onset cerebral small vessel disorder caused by the mutations of the neurogenic locus notch homolog protein 3 (NOTCH 3 ) gene . The extracellular part of NOTCH 3 is composed of 34 epidermal growth factor -like (EGF -like ) repeat domains . Each EGF -like domain is rich of cysteine and glycine to produce three loops that are essential for high -affinity binding to its ligand . Nearly all reported CADASIL -associated mutations result in gain or loss of a cysteine residue within the EGF -like domains . Only a few cysteine-sparing NOTCH 3 mutations have been documented in the patients with CADASIL to date . Here , we reported a Chinese CADASIL family with a cysteine-sparing NOTCH 3 mutation . In this family , affected patients had dizziness , memory loss , gait instability , or hemiplegia . Brain magnetic resonance imaging (MRI ) showed diffuse leukoencephalopathy with confluent signal abnormalities in the periventricular white matter , basal ganglia , and centrum semiovale bilaterally . By screening the entire coding region of NOTCH 3 , a novel missense mutation p .G 149 V (c .446 G >T ) was found . This mutation was not detected in 400 normal controls . Considering the critical position of glycine within the C-loop of EGF -like domain and its high conservation through evolution , p .G 149 V mutation could be a potential pathogenic cause for CADASIL .