FMR1：具有三重面貌的基因。
FMR1: a gene with three faces.
作者信息
Oostra Ben A, Willemsen Rob
机构信息
Department of Clinical Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
出版信息
Biochim Biophys Acta. 2009 Jun;1790(6):467-77. doi: 10.1016/j.bbagen.2009.02.007. Epub 2009 Feb 21.
Abstract
The FMR1 gene is involved in three different syndromes, the fragile X syndrome (FXS), premature ovarian insufficiency (POI) and the fragile X-associated tremor/ataxia syndrome (FXTAS) at older age. Fragile X syndrome is caused by an expansion of a CGG repeat above 200 units in the FMR1 gene resulting in the absence of the FMR1 mRNA and protein. The FMR1 protein is proposed to act as a regulator of mRNA transport and of translation of target mRNAs at the synapse. FXS is seen as a loss of function disorder. POI and FXTAS are found in individuals with an expanded repeat between 50 and 200 CGGs and are associated with increased FMR1 mRNA levels. The presence of elevated FMR1 mRNA in FXTAS suggests that FXTAS may represent a toxic RNA gain-of-function effect. The molecular basis of POI is yet unknown. The role of the FMR1 gene in these disorders is discussed.
摘要
FMR1基因与三种不同的综合征有关，即脆性X综合征（FXS）、卵巢早衰（POI）以及老年时的脆性X相关震颤/共济失调综合征（FXTAS）。脆性X综合征是由FMR1基因中CGG重复序列扩展至200个以上单位引起的，导致FMR1信使核糖核酸（mRNA）和蛋白质缺失。FMR1蛋白被认为在突触处作为mRNA转运和靶mRNA翻译的调节因子发挥作用。FXS被视为一种功能丧失性疾病。POI和FXTAS在CGG重复序列扩展至50至200个之间的个体中出现，且与FMR1 mRNA水平升高有关。FXTAS中FMR1 mRNA水平升高表明，FXTAS可能代表一种毒性RNA功能获得效应。POI的分子基础尚不清楚。文中讨论了FMR1基因在这些疾病中的作用。
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