BACKGROUND Prion diseases are a group of degenerative nerve diseases that are caused by infectious prion proteins or gene mutations.In humans,prion diseases result from mutations in the prion protein gene(PRNP).Only a limited number of cases involving a specific PRNP mutation at codon 196(E196A)have been reported.The coexistence of Korsakoff syndrome in patients with Creutzfeldt-Jakob disease(CJD)caused by E196A mutation has not been documented in the existing literature.CASE SUMMARY A 61-year-old Chinese man initially presented with Korsakoff syndrome,followed by rapid-onset dementia,visual hallucinations,akinetic mutism,myoclonus,and hyperthermia.The patient had no significant personal or familial medical history.Magnetic resonance imaging of the brain revealed extensive hyperintense signals in the cortex,while positron emission tomography/computed tomography showed a diffuse reduction in cerebral cortex metabolism.Routine biochemical and microorganism testing of the cerebrospinal fluid(CSF)yielded normal results.Tests for thyroid function,human immunodeficiency virus,syphilis,vitamin B1 and B12 levels,and autoimmune rheumatic disorders were normal.Blood and CSF tests for autoimmune encephalitis and autoantibody-associated paraneoplastic syndrome yielded negative results.A test for 14-3-3 protein in the CSF yielded negative results.Whole-genome sequencing revealed a diseasecausing mutation in PRNP.The patient succumbed to the illness 11 months after the initial symptom onset.CONCLUSION Korsakoff syndrome,typically associated with alcohol intoxication,also manifests in CJD patients.Individuals with CJD along with PRNP E196A mutation may present with Korsakoff syndrome.
Yong-Kang ZhangJia-Rui LiuKang-Li YinYuan ZongYu-Zhen WangYe-Min Cao
为了探讨云南中甸地区3个地方牛种(中甸牦牛、中甸犏牛、中甸黄牛)朊蛋白基因(PRNP)启动子区和第1内含子区2个位点(23 bp和12 bp)的插入/缺失突变与PRNP基因mRNA表达的相关性,采用聚合酶链式反应、琼脂糖电泳及测序等方法对3个牛种的PRNP基因23 bp和12 bp位点进行基因分型,比较各组间2个位点的等位基因及基因型分布是否存在差异,并进一步采用荧光定量PCR检测延髓组织内PRNP基因表达水平,分析基因型与基因表达水平的关系。结果表明:中甸牦牛的23 bp InDel缺失纯合(-/-)基因型频率最高(0.838),插入等位基因频率极低(0.09),中甸犏牛(0.467)和中甸黄牛(0.399)的缺失纯合基因型频率也较高;而在12 bp InDel中,3种牛的插入纯合(+/+)基因型频率很高,缺失等位基因频率较低;中甸牦牛和中甸犏牛单倍型均以23~-12~+为主,频率为0.794和0.444,而中甸黄牛主单倍型为23^(+)12^(-),频率为0.434。性别、年龄和毛色对3种牛延髓组织中PRNP基因的mRNA表达量无显著影响(P>0.05);3种牛23 bp和12 bp的不同基因型和单倍型之间的mRNA表达量差异均不显著(P>0.05),可能与不同基因型mRNA表达量测定时获得的样品量差异太大有关。研究揭示,23 bp InDel缺失等位基因频率和基因型频率在3种牛中都是最高的,而在12 bp InDel中,缺失等位基因频率和基因型频率均较低,对比以往认为的BSE抗病单倍型23^(+)12^(+),中甸牦牛和中甸犏牛单倍型均以23^(-)12^(+)为主,中甸黄牛以23^(+)12^(-)为主,可通过育种改良筛选,培育对BSE有较高抗病性的群体。
