Skewed X Inactivation in Women Carrying the FMR1 Premutation and Its Relation with Fragile-X-Associated Tremor/Ataxia Syndrome
Skewed X Inactivation in Women Carrying the FMR1 Premutation and Its Relation with Fragile-X-Associated Tremor/Ataxia Syndrome
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DOI：
10.1159/000441566
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发表时间：
2016-01-01
影响因子：
3
通讯作者：
Mila, Montserrat
中科院分区：
文献类型：
--
作者：
Alvarez-Mora, Maria Isabel;Rodriguez-Revenga, Laia;Mila, Montserrat
背景：脆性X相关震颤/共济失调综合征(FXTAS)是一种以意向性震颤和小脑性共济失调为特征的迟发性多系统神经系统疾病。目的：我们假设在患有FXTAS的FMR1前突变女性中，正常的X染色体可能更容易失活，因此，本研究的目的是确定X染色体失活(XCI)与FXTAS的关系。方法：对10例FXTAS患者和21例非FXTAS患者进行FMR1前突变的XCI分析。结果：在FXTAS组和非FXTAS组中，XCI模式的分布在呈现严重偏斜的XCI的等位基因方面存在差异。在FXTAS组中，所有病例优先失活未扩张的X染色体，而在非FXTAS组中，所有病例均失活扩张的X染色体。然而，在比较有无FXTAS的FMR1前突变携带者之间的XCI频率上，没有发现显著差异。正如预期的那样，我们发现，在比较FMR1前突变妇女和对照组时，偏斜的XCI存在统计学上的显著差异。结论：虽然样本量减少和血液XCI模式是本研究的两个局限性，但我们的结果表明正常FMR1等位基因的XCI偏斜可能是FXTAS发生的一个危险因素。此外，我们的发现也支持正常功能磁共振等位基因表达的保护作用。(C)2015年S.Karger AG，巴塞尔
Background: Fragile-X-associated tremor/ataxia syndrome (FXTAS) is a late-onset multisystem neurological disorder characterized by intention tremor and cerebellar ataxia. Objective:We hypothesized that in FMR1 premutation females with FXTAS, a normal X chromosome might more frequently be inactivated; therefore, the aim of this study was to determine the relationship between skewed X chromosome inactivation (XCI) and FXTAS. Methods: We studied the XCI patterns of cases of FMR1 premutation in 10 women with FXTAS and 21 without FXTAS. Results: The distribution of XCI patterns in the FXTAS and no-FXTAS groups showed differences regarding the allele presenting severe skewed XCI. In the FXTAS group, all cases preferentially inactivated the non-expanded X chromosome, whereas in the no-FXTAS group, all inactivated the expanded X chromosome. Nevertheless, no significant differences were found on comparing XCI frequencies among FMR1 premutation carriers with and without FXTAS. As expected, we found statistically significant differences in the skewed XCI on comparing FMR1 premutation women and controls. Conclusion: Although the reduced sample size and blood XCI patterns are two limitations of this study, our results suggest that the skewed XCI of the normal FMR1 allele may be a risk factor for the development of FXTAS. Furthermore, our findings also support the protective effect of the expression of a normal FMRI allele. (C) 2015 S. Karger AG, Basel