Characterization of Prion Disease Associated with a Two-Octapeptide Repeat Insertion.
Characterization of Prion Disease Associated with a Two-Octapeptide Repeat Insertion.
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DOI：
10.3390/v13091794
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发表时间：
2021-09-08
期刊：
影响因子：
--
通讯作者：
Appleby BS
中科院分区：
文献类型：
--
作者：
Brennecke N;Cali I;Mok TH;Speedy H;Genomics England Research Consortium;Hosszu LLP;Stehmann C;Cracco L;Puoti G;Prior TW;Cohen ML;Collins SJ;Mead S;Appleby BS
遗传性朊病毒病占朊病毒病的10-15%。虽然插入四个或更多个八肽重复序列是明确的致病性，但较小的重复序列插入的致病性尚不清楚。该病例系列的目的是提供对2-八肽重复遗传变异特征的深入了解，并提供对无症状携带者克雅氏病风险的深入了解。2-八肽重复插入朊病毒病病例收集自国家朊病毒病病理学监测中心（美国）、国家朊病毒诊所（英国）和国家克雅氏病登记处（澳大利亚）。在三个大规模人群遗传数据库中查询2-八肽重复插入等位基因。8例2-八肽重复插入被确定。这些病例与相同分子亚型的散发性克雅氏病例难以区分。朊病毒蛋白的蛋白质印迹表征的酶消化的情况下，与蛋白酶K显示，2-八肽重复插入和散发性克雅氏病有不同的朊病毒蛋白质的档案。对大规模人群数据集的调查表明，该变异具有很低的变异率。2-八肽重复插入至多是低风险遗传变异。鉴于风险较低，对无症状血亲进行预测性基因检测不太可能是合理的。
Genetic prion disease accounts for 10–15% of prion disease. While insertion of four or more octapeptide repeats are clearly pathogenic, smaller repeat insertions have an unclear pathogenicity. The goal of this case series was to provide an insight into the characteristics of the 2-octapeptide repeat genetic variant and to provide insight into the risk for Creutzfeldt–Jakob disease in asymptomatic carriers. 2-octapeptide repeat insertion prion disease cases were collected from the National Prion Disease Pathology Surveillance Center (US), the National Prion Clinic (UK), and the National Creutzfeldt–Jakob Disease Registry (Australia). Three largescale population genetic databases were queried for the 2-octapeptide repeat insertion allele. Eight cases of 2-octapeptide repeat insertion were identified. The cases were indistinguishable from the sporadic Creutzfeldt–Jakob cases of the same molecular subtype. Western blot characterization of the prion protein in the absence of enzymatic digestion with proteinase K revealed that 2-octapeptide repeat insertion and sporadic Creutzfeldt–Jakob disease have distinct prion protein profiles. Interrogation of large-scale population datasets suggested the variant is of very low penetrance. The 2-octapeptide repeat insertion is at most a low-risk genetic variant. Predictive genetic testing for asymptomatic blood relatives is not likely to be justified given the low risk.
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2.8
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