Characteristics Of NOTCH3 Mutations And Its Clinical Features Of Cadasil Patients

Objectives: To study on characteristics of NOTCH3 mutation and its relationship with cliniclal features of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) patients .Methods: Study on 8 ADASIL patients diagnosed by clinical features and 1 family member asymptomatic. We tested on exons 3,4,5,6,11,12,18,19 of NOTCH3 gene mutation and polymorphism by PCR(Polymerase chain reaction) and sequencing.Results: 5 mutations were found in 6 patients,of which 945delC located on exon 6 was a novel mutation;4 of which was reported before: Arg141Cys,Tyr258Cys,Tyr337Cys and Arg607Cys, locating on exons 4,5,6,11 of NOTCH3 respectively. Arg607Cys was found in 2 patient and 1 family member asymptomatic.The clinical features of Chinese patients were similar with patients repored before,but not exactly the same.In addition,Thr10Thr and Ala202Ala were found in a patient. Mutation was not found in the other two patients.Conclusions: 1.Exon 3,4,6 and 11 may be the hotspots of mutation of NOTCH3 in Chinese population.It suggest that we could test these exons when CADASIL was suspected.2. Different features of clinical presentations of CADASIL were noted between Chinese and Caucasian to some extent.