摘要
目的探讨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(CADASIL)患者的临床特点、病理改变及基因改变。方法对1例CADASIL先证者及其家族共16例的遗传史、临床表现、影像学特点、病理改变及基因改变等方面进行系统研究。结果临床表现为缺血性脑卒中发作、偏头痛、精神异常、痴呆,均无高血压及动脉硬化证据,家系图提示符合常染色体显性遗传;磁共振检查可见皮层下多发腔隙性梗死,脑白质广泛疏松,出现O’Sullivan征及"人"字征;先证者皮肤组织活检示:电镜可见血管平滑肌基底膜存在嗜锇颗粒物质沉积;基因测序显示3例出现Notch3基因第4外显子C144Y突变,其中包括1例颅脑MRI正常的患者。结论该家系可确诊为CADASIL,其致病基因为Notch3基因第4外显子C144Y突变。该家系资料丰富了我国CADASIL家系的资料库。
Objective To explore the clinical presentations,pathological features,imaging manifestation and genetic mutation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL).Methods A systematic study on the clinical manifestations,neuroimaging characteristics,pathology and molecular genetics was performed in the proband and 16 members of the family.An investigation on the hereditary pattern of the family tree of the proband was also conducted.Results The main clinical features including history of ischemic stroke attack,migraine,psychological disoders and dementia were noted.No risk factors of hypertension and arteriosclerosis were found.Pedigree maps of the index case were consistent with classical autosomal dominant inheritance.Subcortical multi-infarct lesions,leukoencephalopathy,O'Sullivan sign and "Herringbone pattern"shape sign were observed via cranial MRI analysis.By electron microscopy,skin biopsy indicated the characteristic deposition of granular osmiophilic material(GOM) on the basement of smooth muscle cells of arterioles in the proband.The mutation of C144Y in the fourth exon of notch 3 gene was revealed in three cases,including 1 patient with normal MRI.Conclusion The pedigree is diagnosed with CADASIL.The main cause can be attributed to a mutation of C144Y in the fourth exon of Notch 3 gene.The pedigree has enriched Chinese database of CADASIL.
出处
《四川大学学报(医学版)》
CAS
CSCD
北大核心
2011年第6期866-869,共4页
Journal of Sichuan University(Medical Sciences)
基金
陕西省自然科学基金(2005C225)资助
关键词
脑动脉疾病
脑白质病
多发性脑梗死
常染色体显性遗传
Cerebral artery diseases Leukoencephalopathy Multi-infarct Autosomal dominant inheritance