理解脆性 X 智力低下震颤/共济失调综合征分子基础的进展。
Advances in understanding the molecular basis of FXTAS.
机构信息
Department of Biochemistry and Molecular Medicine, University of California, Davis, CA, USA.
出版信息
Hum Mol Genet. 2010 Apr 15;19(R1):R83-9. doi: 10.1093/hmg/ddq166. Epub 2010 Apr 29.
Abstract
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder among carriers of premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. The clinical features of FXTAS, as well as other forms of clinical involvement in carriers without FXTAS, are thought to arise from a toxic gain of function of transcriptionally active FMR1 containing expanded CGG repeats. Although the precise mechanisms involved in rCGG toxicity are unknown, here we discuss the latest advances and models that contribute to the understanding of the molecular basis of FXTAS, and the emerging view of FXTAS as the end-stage of a process that begins in early development.
摘要
脆性 X 相关震颤/共济失调综合征（FXTAS）是脆性 X 智力低下 1 基因（FMR1）前突变扩增（55-200 CGG 重复）携带者中发生的一种成年发病的神经退行性疾病。FXTAS 的临床特征，以及无 FXTAS 携带者的其他形式的临床受累，被认为是由转录活性的含有扩增 CGG 重复的 FMR1 的毒性获得性功能引起的。尽管涉及 rCGG 毒性的确切机制尚不清楚，但在这里，我们将讨论有助于理解 FXTAS 的分子基础的最新进展和模型，以及将 FXTAS 视为始于早期发育过程的终末阶段的新观点。
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