Phenotypic variability of Gerstmann-Straussler-Scheinker disease is associated with prion protein heterogeneity
Phenotypic variability of Gerstmann-Straussler-Scheinker disease is associated with prion protein heterogeneity
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DOI：
10.1097/00005072-199810000-00010
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发表时间：
1998-10-01
影响因子：
3.2
通讯作者：
Ghetti, B
中科院分区：
文献类型：
--
作者：
Piccardo, P;Dlouhy, SR;Ghetti, B
Gerstmann-Straussler-Scheinker病（GSS）是一种由朊蛋白基因（PRNP）突变引起的与痴呆相关的小脑锥体综合征，具有表型异质性。造成这种异质性的分子机制尚不清楚。由于我们假设朊病毒蛋白（PrP）的异质性可能与临床病理异质性相关，本研究的目的是分析几种GSS变体中的PrP。在GSS的病理表型中，我们识别出那些没有和有明显海绵状变性的。在后者（即GSS P102 L患者的子集）中，我们观察到ca. 21-30 kDa，与Creutzfeldt-Jakob病中所见相似。相比之下，21-30 kDa亚型在没有海绵状变化的GSS变体中不突出，包括GSS A117 V、GSS D202 N、GSS Q212 P、GSS Q217 R和2例GSS P102 L。这表明GSS中的海绵状变化与这些不同的21-30 kDa亚型的高水平存在有关。不同数量的较小的，不同的PrPres亚型的ca。7-15在所有GSS变体中均观察到kDa。这表明GSS的特征在于存在PrP同种型，其可以部分裂解为低分子量PrPres肽。
Gerstmann-Straussler-Scheinker disease (GSS), a cerebello-pyramidal syndrome associated with dementia and caused by mutations in the prion protein gene (PRNP), is phenotypically heterogeneous. The molecular mechanisms responsible for such heterogeneity are unknown. Since we hypothesize that prion protein (PrP) heterogeneity may be associated with clinico-pathologic heterogeneity, the aim of this study was to analyze PrP in several GSS variants. Among the pathologic phenotypes of GSS, we recognize those without and with marked spongiform degeneration. In the latter (i.e. a subset of GSS P102L patients) we observed 3 major proteinase-K resistant PrP (PrPres) isoforms of ca. 21-30 kDa, similar to those seen in Creutzfeldt-Jakob disease. In contrast, the 21-30 kDa isoforms were not prominent in GSS variants without spongiform changes, including GSS A117V, GSS D202N, GSS Q212P, GSS Q217R, and 2 cases of GSS P102L. This suggests that spongiform changes in GSS are related to the presence of high levels of these distinct 21-30 kDa isoforms. Variable amounts of smaller, distinct PrPres isoforms of ca. 7-15 kDa were seen in all GSS variants. This suggests that GSS is characterized by the presence PrP isoforms that can be partially cleaved to low molecular weight PrPres peptides.