Clinical features of genetic Creutzfeldt-Jakob disease with V180I mutation in the prion protein gene.
Clinical features of genetic Creutzfeldt-Jakob disease with V180I mutation in the prion protein gene.
复制标题
遗传性克鲁特兹菲尔德jakob疾病的临床特征，具有V180i突变，prion蛋白基因。
DOI：
10.1136/bmjopen-2014-004968
复制
发表时间：
2014-05-16
期刊：
影响因子：
2.9
通讯作者：
Mizusawa H
中科院分区：
文献类型：
--
作者：
Qina T;Sanjo N;Hizume M;Higuma M;Tomita M;Atarashi R;Satoh K;Nozaki I;Hamaguchi T;Nakamura Y;Kobayashi A;Kitamoto T;Murayama S;Murai H;Yamada M;Mizusawa H
由于朊蛋白基因（PRNP）V180I突变引起的遗传性克雅氏病（CJD）与散发性克雅氏病及其他遗传性朊蛋白病在临床、病理和生化方面存在差异，引起了人们极大的兴趣。然而，很少有系统的观察这种独特的突变患者的临床特征已发表。因此，本研究的目的是从临床角度将这种突变与其他形式的CJD联系起来。我们分析了患者的临床症状、朊病毒蛋白遗传学、脑脊液（CSF）中的生物标志物和MRI。186例PRNP中V180I突变的日本患者。我们的研究结果表明，V180I突变引起的CJD在老年人，与经典的散发性CJD与甲硫氨酸纯合性密码子129的PRNP相比，具有较慢的进展和较低的可能性发展肌阵挛，小脑，锥体束征和视觉障碍。认知功能障碍是主要症状。弥散加权MRI表现为大脑皮质弥漫性高信号有助于诊断。由于脑脊液中PrPSc的阳性率较低，因此通常需要进行遗传分析以用于与缓慢进行性痴呆的鉴别诊断。我们的结论是，V180I突变PRNP产生一个发展迟缓，发展缓慢，不太严重的形式的CJD，其病变是独特的分布相比，散发性和其他遗传形式的CJD。
Genetic Creutzfeldt-Jakob disease (CJD) due to V180I mutation in the prion protein gene (PRNP) is of great interest because of the differences from sporadic CJD and other genetic prion diseases in terms of clinical features, as well as pathological and biochemical findings. However, few systematic observations about the clinical features in patients with this unique mutation have been published. Therefore, the goal of this study was to relate this mutation to other forms of CJD from a clinical perspective. We analysed clinical symptoms, prion protein genetics, biomarkers in cerebrospinal fluid (CSF) and MRI of patients. 186 Japanese patients with the V180I mutation in PRNP. Our results indicate that the V180I mutation caused CJD at an older age, with a slower progression and a lower possibility of developing myoclonus, cerebellar, pyramidal signs and visual disturbance compared with classical sporadic CJD with methionine homozygosity at codon 129 of PRNP. Cognitive impairment was the major symptom. Diffuse hyperintensity of the cerebral cortex in diffusion-weighted MRI might be helpful for diagnosis. Owing to the low positivity of PrPSc in the CSF, genetic analysis was often required for a differential diagnosis from slowly progressive dementia. We conclude that the V180I mutation in PRNP produces a late-developing and slow-developing, less severe form of CJD, whose lesions are uniquely distributed compared with sporadic and other genetic forms of CJD.
登录
查看更多内容
影响因子：
3.7
作者：
Higuma M;Sanjo N;Satoh K;Shiga Y;Sakai K;Nozaki I;Hamaguchi T;Nakamura Y;Kitamoto T;Shirabe S;Murayama S;Yamada M;Tateishi J;Mizusawa H
通讯作者：
Mizusawa H
影响因子：
3.7
作者：
Xiao X;Yuan J;Haïk S;Cali I;Zhan Y;Moudjou M;Li B;Laplanche JL;Laude H;Langeveld J;Gambetti P;Kitamoto T;Kong Q;Brandel JP;Cobb BA;Petersen RB;Zou WQ
通讯作者：
Zou WQ
影响因子：
4.4
作者：
Iwasaki, Yasushi
通讯作者：
Iwasaki, Yasushi
影响因子：
2.3
作者：
Iwasaki, Yasushi;Mori, Keiko;Hashizume, Yoshio
通讯作者：
Hashizume, Yoshio
影响因子：
64.8
作者：
PALMER, MS;DRYDEN, AJ;COLLINGE, J
通讯作者：
COLLINGE, J