Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Davis, CA 95616, USA.
J Investig Med. 2009 Dec;57(8):825-9. doi: 10.2310/JIM.0b013e3181be329a.
Fragile X-associated tremor/ataxia syndrome is a late adult onset neurodegenerative disorder that affects individuals who carry a premutation CGG repeat expansion (55-200 CGG repeats) in the 5' untranslated portion of the fragile X mental retardation 1 (FMR1) gene. Affected individuals display cognitive decline, progressive intention tremor, gait ataxia, neuropathy, psychiatric symptoms, and parkinsonism; the severity of both clinical and neuropathological phenotypes is positively correlated with the extent of the CGG expansion. Overexpression of the expanded CGG repeat messenger RNA results in a direct gain-of-function cellular toxicity that is believed to form the pathogenic basis for fragile X-associated tremor/ataxia syndrome. This mechanism is entirely different from the mechanism giving rise to fragile X syndrome, which is due to transcriptional silencing and consequent loss of FMR1 protein. Much of the research in the field has focused on understanding the link between the pathogenic FMR1 messenger RNA and the potential proteins that interact with it.
脆性 X 相关震颤/共济失调综合征是一种迟发性成年发病的神经退行性疾病，影响携带脆性 X 智力低下 1 基因（FMR1）5'非翻译区 CGG 重复扩增（55-200 CGG 重复）的个体。受影响的个体表现出认知能力下降、进行性意向震颤、步态共济失调、神经病、精神症状和帕金森病；临床和神经病理学表型的严重程度与 CGG 扩增的程度呈正相关。扩展的 CGG 重复信使 RNA 的过表达导致直接获得功能的细胞毒性，据信这构成了脆性 X 相关震颤/共济失调综合征的致病基础。这种机制与导致脆性 X 综合征的机制完全不同，后者是由于转录沉默和随后的 FMR1 蛋白丢失。该领域的大部分研究都集中在理解致病 FMR1 信使 RNA 与可能与其相互作用的潜在蛋白之间的联系上。
