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一家系的临床及基因研究

The clinical and genetic studies in a family of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

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（cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy，CADASIL）患者的临床特征及基因诊断。方法 对1个CADASIL先证者及其家族的发病情况、遗传方式、临床表现、影像学特征、分子遗传学及治疗等方面进行研究。结果 患者均有记忆力减退、乏力、脑卒中样发作等特点，没有高血压、动脉硬化证据，有家族聚集性，头颅CT、MRI示多发性梗死灶、脑白质变性，临床符合CADASIL的诊断。存活者中基因测序显示NOTCH3基因第3、4外显子突变，可确诊为CADASIL。该家系4代中有3代10人呈临床或亚临床发病，符合常染色体显性遗传。结论 该家系的临床及分子遗传学特征符合CADASIL诊断。

Objective To investigate the clinical features and genetic diagnostic method of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy （CADASIL）. Methods A systematic study on the clinical manifestations, neuroimaging characteristics, therapeutic measures and molecular genetics was performed. An investigation on the onset and hereditary pattern of the family was also done. Results The main clinical features including poor memory and history of stroke were found. And no risk factors of hypertension and arteriosclerosis were found. A positive family history was confirmed. Neuroimaging examination showed multiinfarct lesions and leukoencephalopathy. All these features are in conformity with those of CADASIL. A mutation in the third and fourth exon of the NOTCH3 gene was identified in the 10 cases of 4 generations. The clinical or subclinical onset in the 10 cases was consistent with classical autosomal dominant inheritance. Conclusion The clinical and molecular genetic features of the family accord with CADASIL.