A study of the distributional characteristics of FMR1 transcript levels in 238 individuals
A study of the distributional characteristics of FMR1 transcript levels in 238 individuals
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DOI：
10.1007/s00439-004-1086-x
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发表时间：
2004-04-01
期刊：
影响因子：
5.3
通讯作者：
Sherman, SL
中科院分区：
文献类型：
--
作者：
Allen, EG;He, WY;Sherman, SL
脆性X综合征是遗传性智力低下的最常见形式，是由FMR1基因5'非翻译区CGG重复束的过度扩张和高甲基化引起的。这种甲基化导致基因在转录上沉默。除了重复少于41次的常见等位基因形式外，FMR1基因还有另外两种未甲基化的等位基因形式：预突变（61-200个CGG重复）和中间（41-60个CGG重复）。最近，与脆性X综合征无关的突变前特异性表型已被报道：女性携带者患卵巢早衰（POF）的风险增加20倍，而主要在老年男性携带者中患震颤共济失调综合征（TAS）的风险增加。在分子水平上，在突变前携带者中观察到FMR1转录物水平升高。转录水平的增加可能与POF或TAS表型有因果关系，也可能是一些其他等位基因特性的替代品。在这篇报告中，我们研究了238个个体中按重复大小和性别的转录水平的分布特性。我们已经证实，在男性和女性中，转录水平和重复大小之间存在显著的线性关系。线性效应的证据主要是在突变前大小的等位基因内。
Fragile X syndrome, the most common form of inherited mental retardation, is caused by hyperexpansion and hypermethylation of a CGG repeat tract in the 5' untranslated region of the FMR1 gene. This methylation causes the gene to be transcriptionally silenced. In addition to the common allele form with less than 41 repeats, there are two other allelic forms of the FMR1 gene that are unmethylated: premutation (61-200 CGG repeats) and intermediate (41-60 CGG repeats). Recently, premutation-specific phenotypes not related to fragile X syndrome have been reported: a 20-fold increased risk for premature ovarian failure (POF) among female carriers and an increased risk for a tremor ataxia syndrome (TAS) primarily among older male carriers. At the molecular level, increased levels of FMR1 transcript have been observed among premutation carriers. Increased levels of transcript may be causally related to the POF or TAS phenotypes or may be a surrogate of some other allelic property. In this report, we have examined the distributional properties of transcript levels by repeat size and gender among 238 individuals. We have confirmed a significant linear relationship between transcript level and repeat size in males and females. The evidence for the linear effect is primarily within the premutation size alleles.