Prion protein amyloidosis with divergent phenotype associated with two novel nonsense mutations in PRNP.
Prion protein amyloidosis with divergent phenotype associated with two novel nonsense mutations in PRNP.
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DOI：
10.1007/s00401-009-0609-x
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发表时间：
2010-02
影响因子：
12.7
通讯作者：
Rozemuller AJ
中科院分区：
文献类型：
--
作者：
Jansen C;Parchi P;Capellari S;Vermeij AJ;Corrado P;Baas F;Strammiello R;van Gool WA;van Swieten JC;Rozemuller AJ
编码朊病毒蛋白（PRNP）的基因中的终止密码子突变非常罕见，迄今为止仅在两名患有朊病毒蛋白脑淀粉样血管病（PrP-CAA）的患者中描述。在这份报告中，我们描述的临床，组织病理学和病理性朊蛋白（PrPSc）的特点，两个荷兰患者携带新的相邻终止密码子突变的C-末端部分的PRNP，导致在任何情况下，遗传性朊蛋白淀粉样变性，但有显着不同的临床病理表型。病程最短（27个月）的患者携带Y226 X突变，显示PrP-CAA，无任何神经系统病变，而病程最长（72个月）的患者携带Q227 X突变，显示不寻常的Gerstmann-Sträussler-Scheinker病表型，有许多脑多中心淀粉样斑块和严重的神经系统病变，无PrP-CAA。Western印迹分析表明，在与Q227 X突变的患者存在一个7 kDa的非糖基化的PrPSc片段截短的N-和C-末端。我们的观察扩大了与PRNP突变相关的临床病理表型谱，并表明PrP C-末端的单个酪氨酸残基差异可能会显着影响淀粉样蛋白沉积的位点和朊病毒疾病的整体表型表达。此外，它证实了PrP中糖基磷脂酰肌醇锚的缺乏易导致淀粉样斑块的形成。
Stop codon mutations in the gene encoding the prion protein (PRNP) are very rare and have thus far only been described in two patients with prion protein cerebral amyloid angiopathy (PrP-CAA). In this report, we describe the clinical, histopathological and pathological prion protein (PrPSc) characteristics of two Dutch patients carrying novel adjacent stop codon mutations in the C-terminal part of PRNP, resulting in either case in hereditary prion protein amyloidoses, but with strikingly different clinicopathological phenotypes. The patient with the shortest disease duration (27 months) carried a Y226X mutation and showed PrP-CAA without any neurofibrillary lesions, whereas the patient with the longest disease duration (72 months) had a Q227X mutation and showed an unusual Gerstmann-Sträussler-Scheinker disease phenotype with numerous cerebral multicentric amyloid plaques and severe neurofibrillary lesions without PrP-CAA. Western blot analysis in the patient with the Q227X mutation demonstrated the presence of a 7 kDa unglycosylated PrPSc fragment truncated at both the N- and C-terminal ends. Our observations expand the spectrum of clinicopathological phenotypes associated with PRNP mutations and show that a single tyrosine residue difference in the PrP C-terminus may significantly affect the site of amyloid deposition and the overall phenotypic expression of the prion disease. Furthermore, it confirms that the absence of the glycosylphosphatidylinositol anchor in PrP predisposes to amyloid plaque formation.
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影响因子：
4.2
作者：
Giaccone, G.;Mangieri, M.;Tagliavini, F.
通讯作者：
Tagliavini, F.
DOI：
10.1073/pnas.93.2.744
发表时间：
1996-01-23
影响因子：
11.1
作者：
Ghetti, B;Piccardo, P;Tagliavini, F
通讯作者：
Tagliavini, F
影响因子：
12.7
作者：
TATEISHI, J;KITAMOTO, T;PEIFFER, J
通讯作者：
PEIFFER, J
散发性和遗传性脑淀粉样血管病的遗传学和分子发病机制。
影响因子：
12.7
作者：
Revesz T;Holton JL;Lashley T;Plant G;Frangione B;Rostagno A;Ghiso J
通讯作者：
Ghiso J
影响因子：
6.4
作者：
GHETTI, B;DLOUHY, SR;TAGLIAVINI, F
通讯作者：
TAGLIAVINI, F