Fragile X syndrome
Fragile X syndrome
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DOI：
10.1038/nrdp.2017.65
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发表时间：
2017-09-29
影响因子：
81.5
通讯作者：
Hagerman, Paul J.
中科院分区：
文献类型：
--
作者：
Hagerman, Randi J.;Berry-Kravis, Elizabeth;Hagerman, Paul J.
脆性X综合征（FXS）是智力残疾和自闭症谱系障碍的主要遗传形式，患者除了语言发育不良和癫痫发作外，还可能出现严重的行为改变，包括多动，冲动和焦虑。FXS是一种三核苷酸重复障碍，其中FMR 1中CGG基序的> 200个重复导致基因沉默及其产物脆性X智力低下1蛋白（FMRP）的损失。FMRP在基因表达中具有核心作用，并调节可能数百种mRNA的翻译，其中许多涉及神经元突触连接的发育和维持。事实上，神经可塑性的紊乱是FXS动物模型中的关键发现，并且抑制性和兴奋性神经元回路的不平衡被认为是这种疾病的许多临床表现的基础。我们对FMRP调控的蛋白质的了解正在迅速增长，这导致了治疗干预的多个靶点的鉴定，其中一些已经进入临床试验或临床实践。
Fragile X syndrome (FXS) is the leading inherited form of intellectual disability and autism spectrum disorder, and patients can present with severe behavioural alterations, including hyperactivity, impulsivity and anxiety, in addition to poor language development and seizures. FXS is a trinucleotide repeat disorder, in which > 200 repeats of the CGG motif in FMR1 leads to silencing of the gene and the consequent loss of its product, fragile X mental retardation 1 protein (FMRP). FMRP has a central role in gene expression and regulates the translation of potentially hundreds of mRNAs, many of which are involved in the development and maintenance of neuronal synaptic connections. Indeed, disturbances in neuroplasticity is a key finding in FXS animal models, and an imbalance in inhibitory and excitatory neuronal circuits is believed to underlie many of the clinical manifestations of this disorder. Our knowledge of the proteins that are regulated by FMRP is rapidly growing, and this has led to the identification of multiple targets for therapeutic intervention, some of which have already moved into clinical trials or clinical practice.