Unidad Neurociencias, Instituto de Investigación Biodonostia, San Sebastián, Spain.
Am J Med Genet B Neuropsychiatr Genet. 2010 Oct 5;153B(7):1283-91. doi: 10.1002/ajmg.b.31099.
Transmissible spongiform encephalopathies (TSEs) are a group of rare fatal neurodegenerative disorders. Creutzfeldt-Jakob disease (CJD) represents the most common form of TSE and can be classified into sporadic, genetic, iatrogenic and variant forms. Genetic cases are related to prion protein gene mutations but they only account for 10-20% of cases. Here we report an apparently sporadic CJD case with negative family history carrying a mutation at codon 178 of prion protein gene. This mutation is a de novo mutation as the parents of the case do not show it. Furthermore the presence of three different alleles (wild type 129M-178D and 129V-178D and mutated 129V-178N), confirmed by different methods, indicates that this de novo mutation is a post-zygotic mutation that produces somatic mosaicism. The proportion of mutated cells in peripheral blood cells and in brain tissue was similar and was estimated at approximately 97%, suggesting that the mutation occurred at an early stage of embryogenesis. Neuropathological examination disclosed spongiform change mainly involving the caudate and putamen, and the cerebral cortex, together with proteinase K-resistant PrP globular deposits in the cerebrum and cerebellum. PrP typing was characterized by a lower band of 21 kDa. This is the first case of mosaicism described in prion diseases and illustrates a potential etiology for apparently sporadic neurodegenerative diseases. In light of this case, genetic counseling for inherited and sporadic forms of transmissible encephalopathies should take into account this possibility for genetic screening procedures.
传染性海绵状脑病（TSE）是一组罕见的致命神经退行性疾病。克雅氏病（CJD）是 TSE 中最常见的形式，可分为散发性、遗传性、医源性和变异型。遗传性病例与朊病毒蛋白基因突变有关，但仅占病例的 10-20%。本文报道了一例散发性 CJD 病例，其家族史阴性，携带朊病毒蛋白基因突变，位于密码子 178。该突变是一种从头突变，因为病例的父母没有携带该突变。此外，通过不同方法证实存在三种不同的等位基因（野生型 129M-178D 和 129V-178D 以及突变型 129V-178N），表明该从头突变是一种合子后突变，产生体细胞镶嵌现象。外周血细胞和脑组织中突变细胞的比例相似，约为 97%，提示突变发生在胚胎发育的早期。神经病理学检查显示海绵状改变主要累及尾状核和壳核，以及大脑皮层，同时大脑和小脑有蛋白酶 K 抗性 PrP 球状沉积。PrP 类型特征为 21kDa 的较低条带。这是首例描述的朊病毒病镶嵌现象，说明了一种潜在的病因不明的神经退行性疾病。鉴于该病例，遗传性和散发性传染性脑病的遗传咨询应考虑到这种遗传筛查的可能性。
