CGG repeat in the FMR1 gene: size matters

被引:136
作者
Willemsen, R. [1 ]
Levenga, J. [1 ]
Oostra, B. A. [1 ]
机构
[1] Erasmus MC, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands
关键词
CGG repeat; FMR1; FXPOI; FXTAS; mental retardation; treatment; FRAGILE-X-SYNDROME; MENTAL-RETARDATION PROTEIN; TREMOR/ATAXIA SYNDROME FXTAS; PREMATURE OVARIAN FAILURE; MOUSE MODEL; MESSENGER-RNA; KNOCKOUT MICE; DENDRITIC SPINES; DROSOPHILA MODEL; FULL MUTATION;
D O I
10.1111/j.1399-0004.2011.01723.x
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The FMR1 gene contains a CGG repeat present in the 5'-untranslated region which can be unstable upon transmission to the next generation. The repeat is up to 55 CGGs long in the normal population. In patients with fragile X syndrome (FXS), 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 absence of FMR1 protein, FMRP, seen in FM is the cause of the mental retardation in patients with FXS. The premutation (PM) is defined as 55-200 CGGs. Female PM carriers are at risk of developing primary ovarian insufficiency. Elderly PM carriers might develop a progressive neurodegenerative disorder called fragile X-associated tremor/ataxia syndrome (FXTAS). Although arising from the mutations in the same gene, distinct mechanisms lead to FXS (absence of FMRP), FXTAS (toxic RNA gain-of-function) and FXPOI. The pathogenic mechanisms thought to underlie these disorders are discussed. This review gives insight on the implications of all possible repeat length categories seen in fragile X families.
引用
收藏
页码:214 / 225
页数:12
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