Two different clinical phenotypes of Creutzfeldt-Jakob disease with a M232R substitution
Two different clinical phenotypes of Creutzfeldt-Jakob disease with a M232R substitution
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DOI：
10.1007/s00415-007-0540-9
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发表时间：
2007-11-01
影响因子：
6
通讯作者：
Itoyama, Yasuto
中科院分区：
文献类型：
--
作者：
Shiga, Yusei;Satoh, Katsuya;Itoyama, Yasuto
目的探讨朊蛋白基因（PRNP）第232位密码子（CJD 232）精氨酸取代甲硫氨酸（M232 R取代）所致克雅病的临床特征。患者和方法：我们评估了20例CJD 232患者的临床和实验室特征：发病年龄，初始症状，持续时间，直到成为运动不能和哑巴，持续时间，直到发生周期性的尖锐和波复合脑电图（PSWC），MRI结果，和CSF 14-3-3蛋白的存在。免疫组化，朊病毒蛋白（PrP）沉积进行了研究。结果所有患者均无CJD家族史。我们识别出两种临床表型：快速进展型（rapidtype）和缓慢进展型（slowtype）。在20名患者中，15名患者分别在平均3.1个月、2.4个月和2.8个月内（快速型）出现运动不能和静音、肌阵挛和PSWC。5例表现为缓慢进展的临床病程（缓慢型）。5例出现运动不能和沉默，4例出现肌阵挛，平均持续时间分别为20.6和15.3个月，明显长于快速型。只有1例在发病后13个月表现出PSWC。4例快速型患者表现为弥漫性突触型沉积，2例空泡周围型和弥漫性突触型沉积，1例缓慢型患者表现为弥漫性突触型沉积。50名疑似但非CJD患者中有3人有M232 R替代。结论CJD 232患者与sCJD患者无家族史，尽管具有相同的PRNP基因型，但表现出两种不同的临床表型。需要更多的研究来确定M232 R取代是否导致疾病并影响疾病进展。
Objective To describe the clinical features of Creutzfeldt-Jakob disease with a substitution of arginine for methionine (M232R substitution) at codon 232 (CJD232) of the prion protein gene (PRNP). Patients and methods We evaluated the clinical and laboratory features of 20 CJD232 patients: age of onset, initial symptoms, duration until becoming akinetic and mute, duration until occurrence of periodic sharp and wave complexes on EEG (PSWC), MRI findings, and the presence of CSF 14-3-3 protein. Immunohistochemically, prion protein (PrP) deposition was studied. Results None of the patients had a family history of CJD. We recognized two clinical phenotypes: a rapidly progressive type (rapidtype) and a slowly progressive type (slow-type). Out of 20 patients, 15 became akinetic and mute, demonstrated myoclonus, and showed PSWC within a mean duration of 3.1, 2.4, and 2.8 months, respectively (rapid-type). Five showed slowly progressive clinical courses (slow-type). Five became akinetic and mute and four demonstrated myoclonus within a mean duration of 20.6 and 15.3 months, respectively, which were significantly longer than those in the rapid-type. Only one demonstrated PSWC 13 months after the onset. Diffuse synaptic-type deposition was demonstrated in four rapidtype patients, and perivacuolar and diffuse synaptic-type deposition in two, and diffuse synaptic-type deposition in one slow-type patient. Three of 50 suspected but non-CJD patients had the M232R substitution. Conclusions Patients with CJD232 had no family history like patients with sCJD, and showed two different clinical phenotypes in spite of having the same PRNP genotype. More studies are needed to determine whether M232R substitution causes the disease and influences the disease progression.