1例NOTCH3基因双位点突变致CADASIL报道

doi:10.3969/j.issn.1673-5765.2025.09.014

中国卒中杂志 ›› 2025, Vol. 20 ›› Issue (9): 1186-1192.DOI: 10.3969/j.issn.1673-5765.2025.09.014

1例NOTCH3基因双位点突变致CADASIL报道

陆小燕，黎佳思

上海 200082 海军军医大学第一附属医院神经内科

收稿日期:2024-10-09 修回日期:2025-06-15 接受日期:2025-06-23 出版日期:2025-09-20 发布日期:2025-09-20
通讯作者: 黎佳思 lijiasisissi@163.com

A Case Report of CADASIL Caused by Dual Mutations in the NOTCH3 Gene

LU Xiaoyan, LI Jiasi

Department of Neurology, The First Affiliated Hospital of Naval Medical University, Shanghai 200082, China

Received:2024-10-09 Revised:2025-06-15 Accepted:2025-06-23 Online:2025-09-20 Published:2025-09-20
Contact: LI Jiasi, E-mail: lijiasisissi@163.com

摘要/Abstract

摘要： 伴皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病（cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy，CADASIL）是一种由NOTCH3基因突变引起的遗传性脑小血管病。本文报道1例老年男性CADASIL病例，患者以认知障碍为主要临床表现，伴情绪低落及淡漠。头颅MRI表现为多发腔隙性梗死灶、广泛脑白质变性及颅内多发微出血灶。基因检测提示，NOTCH3基因存在p.A1913V及p.R728C双位点错义杂合突变；三维结构预测分析提示，p.A1913V突变导致蛋白结构中第1913位丙氨酸突变为缬氨酸，p.R728C突变导致蛋白结构中第728位精氨酸突变为半胱氨酸。其中，p.A1913V突变既往尚无相关报道，双位点突变均导致野生型NOTCH3蛋白结构中氨基酸改变，进而改变蛋白质的结构和功能，从而致病。

关键词: 伴皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病; NOTCH3基因; 认知障碍; 脑白质变性

Abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a kind of hereditary cerebral small vessel disease caused by mutations in the NOTCH3 Gene. This article reports a case of an elderly male CADASIL patient who primarily presented with cognitive impairment accompanied by low mood and apathy. Head MRI revealed multiple lacunar infarcts, extensive leukoencephalopathy, and multiple cerebral microbleeds. Genetic testing identified dual NOTCH3 gene mutations, p.A1913V and p.R728C. Three-dimensional structural prediction analysis indicated that the p.A1913V mutation results in the substitution of alanine with valine at position 1913 in the protein structure, and the p.R728C mutation leads to the substitution of arginine with cysteine at position 728 in the protein structure. The p.A1913V mutation has not been previously reported. Both mutations lead to amino acid changes in the wild-type NOTCH3 protein structure, thereby altering the protein’s structure and function, ultimately causing the disease.

Key words: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; NOTCH3 gene; Cognitive impairment; Leukoencephalopathy

中图分类号:

R74
R459.7

陆小燕, 黎佳思. 1例NOTCH3基因双位点突变致CADASIL报道[J]. 中国卒中杂志, 2025, 20(9): 1186-1192.

LU Xiaoyan, LI Jiasi. A Case Report of CADASIL Caused by Dual Mutations in the NOTCH3 Gene[J]. Chinese Journal of Stroke, 2025, 20(9): 1186-1192.

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1例NOTCH3基因双位点突变致CADASIL报道

A Case Report of CADASIL Caused by Dual Mutations in the NOTCH3 Gene

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