Australian National CJD Registry, Department of Pathology, The University of Melbourne, Parkville 3010, Australia.
Neurosci Lett. 2010 Mar 12;472(1):16-8. doi: 10.1016/j.neulet.2010.01.043. Epub 2010 Jan 25.
Precedent of causative multiplication of key gene loci exists in familial forms of both Alzheimer's and Parkinson's diseases. Genetic Creutzfeldt-Jakob disease (CJD) is often clinically indistinguishable from sporadic disease and inexplicably, a negative family history of a similar disorder occurs in around 50-90% of patients harboring the most common, disease-associated, prion protein gene (PRNP) mutations. We undertook semi-quantitative analysis of the PRNP copy number in 112 CJD patients using quantitative polymerase chain reaction. All included cases satisfied classification criteria for probable or definite sporadic CJD, ascertained as part of longstanding, prospective, national surveillance activities. No examples of additional copies of the PRNP locus as an explanation for their disease was found in any of the 112 sporadic CJD patients. Hence, contrasting with more common, age-related neurodegenerative diseases, the genetic aetiology in human prion disease continues to appear entirely restricted to small scale mutations within a single gene, with no evidence of multiplication of this validated candidate gene locus as a cause.
阿尔茨海默病和帕金森病的家族形式中存在关键基因座的因果倍增先例。遗传 Creutzfeldt-Jakob 病 (CJD) 在临床上常常与散发性疾病无法区分，而且令人费解的是，大约 50-90%携带最常见的、与疾病相关的朊病毒蛋白基因 (PRNP) 突变的患者存在无类似疾病家族史。我们使用定量聚合酶链反应对半定量分析了 112 例 CJD 患者的 PRNP 拷贝数。所有纳入的病例均符合可能或确定的散发性 CJD 的分类标准，作为长期、前瞻性国家监测活动的一部分确定。在 112 例散发性 CJD 患者中，均未发现 PRNP 基因座的额外拷贝可以解释其疾病。因此，与更常见的年龄相关神经退行性疾病不同，人类朊病毒病的遗传病因似乎完全局限于单个基因中的小规模突变，没有证据表明该已验证候选基因座的倍增是病因。
