T188K突变的10例遗传型克雅病患者的临床及家族特征分析  

Clinical characteristics of 10 familial clustering cases of Creutzfeldt-Jakob disease with T188K mutation in China

作　　者：周伟[1] 陈操[1] 王吉春[1] 张晓美[1] 董小平[1] 石琦[1] 

机构地区：[1]中国疾病预防控制中心病毒病预防控制所 传染病预防控制国家重点实验室,北京102206

出　　处：《中国病毒病杂志》2013年第4期280-283,共4页Chinese Journal of Viral Diseases

基　　金：传染病预防控制国家重点实验室基金(2012SKLID102;2011SKLID211);中国疾病预防控制中心青年科研基金(2012A102)

摘　　要：目的对自2006年开始克雅病监测网络监测到的10例T188K突变的遗传型克雅病确诊病例进行了临床特征及家族信息的分析。方法应用基因测序的方法发现了不同克雅病病例PRNP基因T188K的突变,应用Western Blot方法对脑脊液中14-3-3蛋白进行检测,并根据世界卫生组织(WHO)推荐的克雅病诊断标准对报告病例进行了诊断,对其主要临床特征及家族信息进行了分析。结果自2006年克雅病监测网络开始监测,已有10例T188K突变的遗传型克雅病病例被确诊。这些病例的平均发病年龄为58.8岁(40～76岁),其首发症状是多种多样的,包括快速进行性痴呆、精神症状、小脑共济失调及走路不稳的症状等。主要的临床症状与散发型克雅病相似,快速进行性痴呆在所有病例中均出现。病例的平均病程为4.5个月。只有1个病例出现典型的周期性脑电图三相波。共有6例病例核磁共振成像(MRI)出现皮层及(或)尾状核异常高信号。脑脊液14-3-3蛋白在10个病例中的8例出现阳性。只有2例病例出现与疾病相关的家族史。结论这些资料说明T188K突变在中国的遗传型克雅病病例中具有相对较高的频率,同时这些病例与散发型克雅病有着比较相近的临床表现。Objective To analyze the characteristics of 10 familial cases of Creutzfeidt-Jakob disease （CJD） in China and study the mutations in the prion protein gene （PRNP）. Methods CJD patents were recruited from the CJD surveillance network of China since 2006. Final diagnosis was based on the WHO-recommended cri- teria. Familial clustering was confirmed by the familial disease history of this disease and PRNP gene sequen- cing was done for these cases. Results A total of 10 CJD cases were identified as familial clustering cases with T188K mutation in their PRNP gene. The median age of these 10 eases at onset was 58.8 （40-76） years old. The foremost symptoms were various, including rapid progressive dementia, mental symptoms, cerebel lar ataxia and movement disturbances. The main symptoms of these familial CJD eases were similar to that of sporadic CJD patients especially that rapid progressive dementia was found in all cases. The median duration of the disease was 4.5 months. Typical electroencephalogram （EEG） changes was noticed in only one case; 6 patients showed strong signals in caudate/putamen with the Magnetic Resonance Imaging （MRI） brain scan. 14-3-3 protein in cerebrospinal fluid （CSF） was detected positive in 8 out of 10 tested patients. Clearfamily history was investigated in only 2 patients. Conclusions Familial CJD patients with T188K mutation of the PRNP gene demonstrated similar clinical characteristics as that of sporadic CJD, The T188K mutation of the PRNP gene is more common in Chinese CJD patients.

关 键 词：遗传型克雅病 T188K PRNP基因 14-3-3蛋白 

分 类 号：R742.9[医药卫生—神经病学与精神病学]