NOTCH3 gene mutations in two Chinese families featuring cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy.
- VernacularTitle:两个伴皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病家系NOTCH3基因的突变分析
- Author:
Qiying SUN
1
;
Wenwen LI
;
Yafang ZHOU
;
Fang YI
;
Jianfeng WANG
;
Yacen HU
;
Lingyan YAO
;
Lin ZHOU
;
Hongwei XU
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Brain; diagnostic imaging; CADASIL; diagnostic imaging; genetics; Female; Heterozygote; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; Receptor, Notch3; genetics
- From: Chinese Journal of Medical Genetics 2017;34(6):816-820
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo analyze potential mutations of the NOTCH3 gene in two Chinese families featuring cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy (CADASIL).
METHODSThe two probands and related family members and 100 healthy controls were recruited. Potential mutations of the NOTCH3 gene were screened by PCR and direct sequencing. PolyPhen-2 and SIFT software were used to predict the protein function.
RESULTSThe conditions of both probands were adult-onset, with main clinical features including recurrent transient ischemic attacks and/or strokes, cognitive impairment. MRI findings suggested multiple cerebral infarcts and severe leukoencephalopathy. A heterozygous mutation c.328C>T (p.Arg110Cys), which was located in exon 3 of the NOTCH3 gene and known as a causative mutation, was identified in proband 1. A novel heterozygous mutation c.1013 G>C (p.Cys338Ser) located in exon 6 of the NOTCH3 gene was identified in the proband 2, which was not reported previously. The same mutations were not detected among the 100 unrelated healthy controls. Function analysis suggested that heterozygous mutation c.1013G>C can severely affect the functions of NOTCH3 protein.
CONCLUSIONTwo heterozygous missense mutations in the NOTCH3 gene have been identified in two families affected with CADASIL. The novel heterozygous Cys338Ser mutation in exon 6 of the NOTCH3 gene probably underlies the CADASIL.