HOMOZYGOUS PRION PROTEIN GENOTYPE PREDISPOSES TO SPORADIC CREUTZFELDT-JAKOB DISEASE
HOMOZYGOUS PRION PROTEIN GENOTYPE PREDISPOSES TO SPORADIC CREUTZFELDT-JAKOB DISEASE
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DOI：
10.1038/352340a0
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发表时间：
1991-07-25
期刊：
影响因子：
64.8
通讯作者：
COLLINGE, J
中科院分区：
文献类型：
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作者：
PALMER, MS;DRYDEN, AJ;COLLINGE, J
人类朊病毒疾病，克雅氏病（CJD）和格斯特劳斯勒综合征（GSS），是一种具有传染性和遗传性的神经退行性疾病。这两种疾病和动物海绵状脑病（例如，痒病和牛海绵状脑病）通过脑内接种脑匀浆传染给实验动物已得到充分记录。尽管在实验中具有遗传性，但朊蛋白基因的错义和插入突变与GSS和家族性CJD都相关，这表明人类家族性病例是常染色体显性疾病2-6。然而，超过80%的CJD病例是零星发生的，并且不知道与突变有关。22例散发性克雅氏病病例中有21例，23例疑似散发性克雅氏病病例中有19例多态性氨基酸残基129为纯合；51%的正常人群在这个位点是杂合的。我们认为纯合子倾向于散发性克雅氏病，这直接支持了朊病毒蛋白分子之间相互作用是疾病过程基础的假设。
THE human prion diseases, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler syndrome (GSS), are neurodegenerative diseases that are unique in being both infectious and genetic. Transmission of both diseases and the animal spongiform encephalopathies (for example, scrapie and bovine spongiform encephalopathy) to experimental animals by intracerebral inoculation with brain homogenates is well documented 1. Despite their experimental transmissibility, missense and insertional mutations in the prion protein gene are associated with both GSS and familial CJD, demonstrating that the human familial cases are autosomal dominant diseases 2-6. More that 80% of CJD cases occur sporadically, however, and are not known to be associated with mutations. Here we report that 21 of 22 sporadic CJD cases and a further 19 of 23 suspected sporadic CJD cases are homozygous at the polymorphic amino-acid residue 129; 51% of the normal population are heterozygous at this site. We argue that homozygosity predisposes towards sporadic CJD and that this directly supports the hypothesis that interaction between prion protein molecules underlies the disease process.