The FMR1 gene and fragile X-associated tremor/ataxia syndrome.
The FMR1 gene and fragile X-associated tremor/ataxia syndrome.
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DOI：
10.1002/ajmg.b.30910
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发表时间：
2009-09-05
影响因子：
2.8
通讯作者：
Oostra, B. A.
中科院分区：
文献类型：
--
作者：
Brouwer, J. R.;Willemsen, R.;Oostra, B. A.
存在于FMR 1基因5′UTR的CGG重复序列在传递给下一代时是不稳定的。在正常人群中，重复序列长达55 CGG。在脆性X染色体患者中，重复长度超过200 CGG（完全突变：FM）通常会导致重复序列和启动子区域的甲基化，并伴随着FMR 1基因的沉默。基因产物FMRP参与调节树突中某些mRNA的转运和翻译，从而影响突触可塑性。这是学习和记忆过程的核心。FM中FMRP的缺失是脆性X患者智力低下的原因。前突变（PM）定义为55-200 CGG。女性PM携带者有发生原发性卵巢功能不全的风险。最近发现，老年PM携带者可能会发展为一种进行性神经退行性疾病，称为脆性X相关震颤/共济失调综合征。虽然由同一基因的突变引起，但不同的机制导致脆性X综合征（缺乏FMRP）和FXTAS（毒性RNA功能获得）。被认为是这些疾病的致病机制进行了讨论，特别强调FXTAS。这篇评论提供了洞察力的影响，所有可能的重复长度类别中看到的脆性X家族。
The CGG-repeat present in the 5′UTR of the FMR1 gene is unstable upon transmission to the next generation. The repeat is up to 55 CGGs long in the normal population. In fragile X patients, a repeat length exceeding 200 CGGs (full mutation: FM) generally leads to methylation of the repeat and the promoter region, which is accompanied by silencing of the FMR1 gene. The gene product FMRP is involved in regulation of transport and translation of certain mRNA in the dendrite, thereby affecting synaptic plasticity. This is central to learning and memory processes. The absence of FMRP seen in FM is the cause of the mental retardation seen in fragile X patients. The premutation (PM) is defined as 55–200 CGGs. Female PM carriers are at risk of developing primary ovarian insufficiency. Recently it was discovered that elderly PM carriers might develop a progressive neurodegenerative disorder called fragile X-associated tremor/ataxia syndrome. Although arising from the mutations in the same gene, distinct mechanisms lead to fragile X syndrome (absence of FMRP) and FXTAS (toxic RNA gain of function). The pathogenic mechanisms thought to underlie these disorders are discussed, with a specific emphasis on FXTAS. This review gives insight on the implications of all possible repeat length categories seen in fragile X families.
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影响因子：
11
作者：
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通讯作者：
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作者：
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作者：
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Oostra, BA
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作者：
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通讯作者：
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