Jansen C, van Swieten J C, Capellari S, Strammiello R, Parchi P, Rozemuller A J M
Dutch Surveillance Centre for Prion Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands.
J Neurol Neurosurg Psychiatry. 2009 Dec;80(12):1386-9. doi: 10.1136/jnnp.2008.169359.
An atypical case of inherited Creutzfeldt-Jakob disease (CJD) is described in a 35-year-old Dutch woman, homozygous for methionine at codon 129 of the prion protein gene (PRNP). The clinical phenotype was characterised by slowly progressive cognitive decline and parkinsonism. Neuropathological findings consisted of scanty spongiosis and only faint to absent immunohistochemical staining for the abnormal prion protein, PrP(Sc), with patchy deposits in the cerebellar cortex. Purkinje cells were abnormally located in the molecular layer of the cerebellum. Western blot analysis showed the co-occurrence of PrP(Sc) types 1 and 2 with an unusual distribution. Sequence analysis disclosed a novel 120 bp insertion in the octapeptide repeat region of the PRNP, encoding five additional R2 octapeptide repeats. These features define an unusual neuropathological phenotype and novel genotype, further expanding the spectrum of genotype-phenotype correlations in inherited prion diseases and emphasising the need to carry out pre-mortem PRNP sequencing in all young patients with atypical dementias.
本文描述了一名35岁荷兰女性的非典型遗传性克雅氏病（CJD）病例，该女性朊蛋白基因（PRNP）第129密码子为甲硫氨酸纯合子。临床表型的特征为缓慢进展的认知功能减退和帕金森综合征。神经病理学发现包括少量海绵状变性，异常朊蛋白PrP(Sc)的免疫组化染色仅呈弱阳性或缺失，在小脑皮质有斑片状沉积。浦肯野细胞在小脑分子层中的位置异常。蛋白质印迹分析显示PrP(Sc) 1型和2型同时出现，且分布异常。序列分析揭示PRNP八肽重复区域有一个120 bp的新插入片段，编码另外五个R2八肽重复序列。这些特征定义了一种不寻常的神经病理表型和新的基因型，进一步扩大了遗传性朊病毒病基因型-表型相关性的范围，并强调了对所有非典型痴呆的年轻患者进行生前PRNP测序的必要性。
