4个具有相同突变的CADASIL家系临床特征分析

Clinical features of four CADASIL pedigrees sharing the same mutation

目的分析总结4个来自河南地区不同家系但具有相同突变的伴有皮质下梗死和白质脑病常染色体显性遗传性脑动脉病(cerebral autosomal dominantarteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)家系的影像学表现及临床特征,调查家系成员的发病情况。方法回顾性分析4个CADASIL家系先证者的影像学特征和临床特征,调查4个家系中其他成员的发病情况,对患者行Notch3基因3、4、11、18号外显子突变检测,并进行分析。结果4例先证者均以单侧肢体无力为始发症状,其中2例有高血压病史,1例合并糖尿病,1例身体健康;1例有高血压病患者影像学提示丘脑出血,患者无相关主诉;基因检测发现4例先证者及部分家系成员存在p.R607C突变位点。结论存在p.R607C突变位点的4例CADASIL患者临床上首发症状相似,但不同家系成员间存在个体化差异;高血压、糖尿病等脑血管病危险因素可存在于CADASIL患者。

Objective To analyze the clinical and imaging characteristics of cerebral autosomal dominantarteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)in four pedigrees from Henan with the same mutation to investigate the incidence of their family members.Methods The clinical and imaging characteristics of four probands from four CADASIL families were retrospectively analyzed and the members of four families were recruited.DNA sequencing techniques were applied to search for the mutation in exon 3,4,11 and 18of the Notch3.Results In 4probands with the initial symptom of unilateral limb weakness,2probands had history of hypertension,1had history of diabetes mellitus,and 1was healthy.MRI showed thalamic hemorrhage in 1proband with no clinical complaints.One missense mutation p.R607 Cwas found in these four probands and some of their family members.Conclusion These four probands have similar initial symptom,and each of them has his own features.The risk factors for cerebrovascular disease as hypertension and diabetes may be the risk factors for CADASIL.