[Clinicopathological characteristics of Creutzfeldt-Jakob disease with a PrP V180I mutation and M129V polymorphism on different alleles].
[Clinicopathological characteristics of Creutzfeldt-Jakob disease with a PrP V180I mutation and M129V polymorphism on different alleles].
复制标题
不同等位基因PrP V180I突变和M129V多态性克雅氏病的临床病理特征
DOI：
--
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
M. Yamada
中科院分区：
文献类型：
--
作者：
Y. Iwaski;M. Sone;T. Kato;E. Yoshida;T. Indo;M. Yoshida;Y. Hashizume;M. Yamada
我们报告一位80岁的日本男性与组织学诊断克雅氏病（CJD）。患者因突发性运动失语样症状及右半瘫而入住神经内科。他的病史和家族史都很普通，也没有服用任何药物。尿液、血液计数和血液化学都在正常范围内。脑脊液除神经元特异性烯醇化酶升高（29.9 ng/ml）外，其余正常。t2加权MRI图像显示左侧颞叶皮层高信号强度，病变在疾病初期肿胀。Gd-DTPA无增强作用。连续MRI显示高信号病变已扩散至双侧大脑皮层。患者在发病6个月内出现肌阵挛，随后出现运动性缄默症。连续脑电图显示无周期性同步放电（PSD）。他在入院21个月后死于肺炎。尸检显示大脑皮层海绵状改变，伴有库鲁斑块，证实了CJD的诊断。小脑皮层保存完好。高信号病变与大脑皮层海绵状改变相对应。免疫组化分析显示突触朊病毒染色较弱。利用聚合酶链反应、限制性片段长度多态性和直接测序等方法对尸检脑基因组DNA进行PrP基因分析，发现在不同等位基因上密码子180处存在点突变（Val—>Ile）和密码子129处存在多态性（Met/Val）。少数克雅氏病患者的PrP基因密码子180点突变已被报道。密码子180点突变和密码子129多态性的结合可能产生一种不典型的CJD临床病理形式，包括迟发性、PSD阴性和不典型的MRI表现，并保留小脑皮层。
We report an 80-year-old Japanese man with histologically-diagnosed Creutzfeldt-Jakob disease (CJD). The patient was admitted to our neurological unit because of sudden onset motor aphasia-like symptoms and right hemiparesis. His medical and family histories were unremarkable, and he had taken no medications. Urine, blood counts and blood chemistry were all within normal limits. Cerebrospinal fluid was normal except for elevation of neuron specific enolase (29.9 ng/ml). High-signal intensity was demonstrated in the cortex of the left temporal lobe on T2-weighted MRI images, and the lesion swelled during the initial stage of the disease. There was no enhancement with Gd-DTPA. Serial MRI showed that the high-signal lesion had spread into the bilateral cerebral cortex. The patient developed myoclonus followed by akinetic mutism within 6 months of onset. Consecutive EEGs revealed no periodic synchronous discharge (PSD). He died of pneumonia 21 months after of admission. Autopsy revealed spongiform changes in the cerebral cortex with Kuru plaques, confirming the diagnosis of CJD. The Cerebellar cortex was well preserved. The high-signal lesions corresponded to the spongiform changes in the cerebral cortex. Immunohistochemical analysis showed weak synaptic prion staining. Prion protein (PrP) gene analysis of genomic DNA isolated from the autopsied brain by polymerase chain reaction, the restriction fragment length polymorphisms, and direct sequencing revealed a point mutation (Val-->Ile) at codon 180 and a polymorphism (Met/Val) at codon 129 on different alleles. A few CJD patients with point mutations in codon 180 of the PrP gene have been reported. Combination of the codon 180 point mutation and codon 129 polymorphism may yield an atypical clinicopathological form of CJD that includes late onset, negative PSD, and atypical MRI findings, with preservation of the cerebellar cortex.