Progress in hereditary tauopathies: a mutation in the Tau gene (G389R) causes a Pick disease-like syndrome.
Progress in hereditary tauopathies: a mutation in the Tau gene (G389R) causes a Pick disease-like syndrome.
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遗传性 tau 病的进展：Tau 基因 (G389R) 的突变导致匹克病样综合征。
DOI：
10.1111/j.1749-6632.2000.tb06905.x
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发表时间：
2000
影响因子：
5.2
通讯作者：
Goedert,M
中科院分区：
文献类型：
--
作者：
Ghetti,B;Murrell,JR;Zolo,P;Spillantini,MG;Goedert,M
摘要：我们描述了 Taugene 13 号外显子 G389R 突变的临床和病理表型。进行性失语和记忆障碍是最初的症状，开始于四十岁或五十岁，随后出现冷漠、冷漠、食欲亢进、僵硬、锥体征和痴呆。两到五年后就会死亡。磁共振成像和神经病理学研究显示额叶和颞叶萎缩。分别在新皮质和皮质下白质中发现的体状和轴突丝状包涵体具有 tau 免疫反应性。肌氨酰不溶性 tau 蛋白的免疫印迹分析显示了 60 和 64 kDa 的两个主要条带，它们在去磷酸化后分解成三个和四个重复亚型的四个条带。孤立的 tau 蛋白丝通常是直的，偶尔是扭曲的。重组突变 tau 蛋白显示促进微管组装的能力降低，表明这可能是突变的主要影响。目前的研究结果表明，Taucan 中的 G389R 突变会导致与匹克氏病相似的痴呆症。
Abstract:We describe the clinical and pathologic phenotypes of the G389R mutation in exon 13 of theTaugene. Progressive aphasia and memory disturbance are the initial signs and begin in the fourth or fifth decade of life, followed by apathy, indifference, hyperphagia, rigidity, pyramidal signs and dementia. Death occurs after two to five years. Magnetic resonance imaging and neuropathologic studies show frontal and temporal atrophy. Pick body‐like and axonal filamentous inclusions found in the neocortex and subcortical white matter, respectively, are tau immunoreactive. Immunoblot analysis of sarkosyl‐insoluble tau shows two major bands of 60 and 64 kDa that, upon dephosphorylation, resolve into four bands of three‐ and four‐repeat isoforms. Isolated tau filaments are often straight and occasionally twisted. Recombinant mutant tau protein shows a reduced ability to promote microtubule assembly, suggesting that this may be the primary effect of the mutation. The present findings indicate that the G389R mutation inTaucan cause a dementia similar to that in Pick's disease.