【摘要】 目的探讨NOTCH3基因14号外显子基因突变的伴皮质下梗死和白质脑病的常染色体显性遗传性脑病(CADASIL)的临床特征。方法对1例NOTCH3基因14号外显子基因突变的CADASIL患者及其家系的临床资料进行回顾性分析。结果先证者20多岁起出现剧烈的偏头痛样发作,近2年来反复出现头晕、双下肢无力,并伴有兴趣减退、焦虑不安,无明显智能减退。头颅MRI显示双侧基底节区、皮质下及脑干多发缺血梗死灶,并在基底节区和丘脑可见多发微出血病灶。皮肤活检见真皮小血管基底膜增厚及嗜锇颗粒物质。NOTCH3基因突变分析发现14号外显子C2182T突变。家族中有类似患者多例,另有4名亲属检出同样位点的基因突变。结论 14号外显子C2182T突变CADASIL的临床表现主要为偏头痛、情感障碍和反复皮质下脑缺血发作,认知功能减退可能出现较晚。MRI特征为颅内多发白质高信号及微出血病灶,皮肤活检可见嗜锇颗粒物质。NOTCH3基因检测可发现突变。更多还原

【Abstract】 Objective To investigate the clinical manifestations of cerebral autosomal dominant hereditary encephalopathy with subcortical infarcts and leukoencephalopathy( CADASIL) of NOTCH3 gene mutations. Methods The clinical data of one CADASIL of NOTCH3 gene mutations proband and his family were analyzed retrospective.Results The proband had migraine without aura in his twenties. In the past two years,vertigo,limb weakness came up repeatedly combined with interest drops and anxiety symptoms,without apparent progressive memory impairment.A cranial MRI revealed multiple ischemic lesions involving bilateral basal ganglia,subcortex and brain stem,numerous cerebral microbleeds( MBs) were showed in basal ganglia and thalamus. Ganular osmiophilic material( GOM) was detected in the patient,with thicker lamina elastic interna by skin biopsies. Genetic analysis revealed a pathogenic rare C2182 T mutation on exon 14 of the NOTCH3. The family had many similar patients,four relatives were detected with the same gene mutation. Conclusions The main clinical manifestations of CADASIL with C2182 T mutation on exon 14 includes migraine,mood disturbance and subcortical ischemic events,progressive cognitive impairment may come up later. Cranial MRI revealed multiple white matter hyperintensity and multiple microbleeds. Skin biopsy ultrastructure is positive for GOM. The diagnosis of CADASIL is confirmed by genetic testing of NOTCH3.更多还原