title: The genetic spectrum and the evaluation of CADASIL screening scale in Chinese patients with NOTCH3 mutations.
abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small artery disease caused by NOTCH3 gene mutation. Here we report clinical, pathological and genetic profiles of 29 newly-diagnosed CADASIL patients, evaluation of the CADASIL scale in Chinese CADASIL patients, and reanalysis of all reported mainland Chinese patients with identified NOTCH3 gene mutation. We found two novel mutations (p.C134G and p.C291Y) and 13 reported NOTCH3 mutations in the newly-diagnosed group. CADASIL scale score was less than the cutoff score in 19 of 53 Chinese patients with NOTCH3 mutation, generating only a sensitivity of 64.1%. At the time of study, the total number of genetically confirmed CADASIL cases reached 158 from 97 unrelated mainland Chinese families, with 9/97 (9.3%) sporadic patients. The NOTCH3 gene mutation profile showed 43 mutations, with hotspots in exon 4, followed by exon 3. The considerable variability in onset age and CADASIL scale score in patients carrying the same NOTCH3 missense mutation suggested no obvious phenotype-genotype correlation. In conclusion, we report two novel mutations which expand the NOTCH3 mutational spectrum. Exons 4 and 3 are hotspots in mainland Chinese patients with NOTCH3 mutation. The low sensitivity of CADASIL scale in our patients group indicated that the CADASIL scale should be refined according to the clinical characteristics of Chinese CADASIL patients when used in Chinese populations.
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China.
authors.forename: Yuehuan
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China.
authors.forename: He
authors.initials: H
authors.lastname: Lv
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China.
authors.forename: Yining
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Radiology, Peking University First Hospital, Beijing, China.
authors.forename: Jiangxi
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China. Electronic address: yuanyun2002@sohu.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China. Electronic address: drwangzx@163.com.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D046589:CADASIL / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005820:Genetic Testing / Q000379:methods / Q000592:standards*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics*; D055815:Young Adult
chemical_list: C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch
keywords: CADASIL; CADASIL scale; Mainland China; NOTCH3 gene; Novel mutation