NOTCH3基因C260S位点突变导致CADASIL的临床和影像学特征分析  

Analysis of clinical and imaging features of CADASIL caused by a C260S mutation of NOTCH3 gene

作　　者：孔秀云[1] 代飞飞[1] 王佳伟[1] 崔世磊[1] Kong Xiuyun;Dai Feifei;Wang Jiawei;Cui Shilei(Department of Neurology,Beijing Tongren Hospital,Capital Medical University,Beijing 100730,China)

机构地区：[1]首都医科大学附属北京同仁医院神经内科,100730

出　　处：《北京医学》2024年第5期380-384,共5页Beijing Medical Journal

摘　　要：目的探讨NOTCH3基因第5外显子C260S位点突变导致的伴有皮层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)家系的临床和影像学特征。方法选取2021年12月首都医科大学附属北京同仁医院来自同一家庭的CADASIL患者,对所有患者进行NOTCH3基因测序,回顾性分析患者的临床表现和头颅影像学特征。复习既往文献报道的导致同一位置氨基酸改变的其他突变类型的临床及影像学特征。结果4名家庭成员中,包括先证者(46岁,女)及其两个姐姐(分别为48岁和50岁)和女儿(18岁)。先证者及其父亲、两个姐姐都有偏头痛病史,其中大姐有记忆力减退;先证者患有脑梗死及伴有视觉先兆的偏头痛;先证者女儿体健;先证者父亲因脑梗死去世。4名家庭成员均存在C260S位点的NOTCH3基因突变。既往文献无此位点突变的报道,先证者头颅MRI示右侧脑桥亚急性梗死,颞叶、脑室周围及脑干异常高信号改变,其大姐脑桥可见腔隙性梗死灶。结论NOTCH3基因第5外显子c.778T>A(p.C260S)的罕见突变导致的CADASIL发病时间早,早期会出现认知障碍。合并偏头痛的脑干梗死患者,需警惕CADASIL的可能。Objective To explore the clinical and imaging features of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)caused by a C260S mutation in exon 5 of the NOTCH3 gene.Methods Paitents with CADASIL from the same family in Beijing Tongren Hospital affiliated to Capital Medical University in December 2021 were selected.NOTCH3 gene sequencing was performed in the four patients,and the clinical manifestations and cranial imaging features were analyzed retrospectively.Other mutation types that lead to amino acid changes in the same position reported in previous articles were reviewed,and the clinical and imaging features were analyzed as well.Results The four family members included the proband(46-year-old,female),her two elder sisters(48-year-old and 50-year-old,respectively)and her daughter(18-year-old).The proband,her father and her two sisters all had a history of migraine,and the elder sister had memory loss.The proband had previous cerebral infarction and migraine with visual aura.The daughter of the proband was healthy,and the proband's father died of cerebral infarction.The C260S NOTCH3 mutation was present in all the four family members.There was no report of mutation at this site in previous literature.The proband's cranial MRI showed subacute infarction on the right pontine,abnormal high signal changes in temporal lobe,periventricular and brain stems.The elder sister's MRI showed lacunar infarction on the pons.Conclusions The rare mutation of c.778T>A(p.C260S)in exon 5 of NOTCH3 gene leads to the early onset of CADASIL,and cognitive impariment will occur in the early stage.Patients with brainstem infarction combined with migraine should be considered of the possibility of CADASIL.

关 键 词：伴有皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病 NOTCH3 C260S 第5外显子 

分 类 号：R743[医药卫生—神经病学与精神病学]