Center for Diagnosis and Treatment of Fragile X Syndrome (CDTSXF), INTA University of Chile, Santiago, Chile.
Clin Genet. 2014 Oct;86(4):378-82. doi: 10.1111/cge.12278. Epub 2013 Oct 13.
Carriers of an FMR1 premutation allele (55-200 CGG repeats) often develop the neurodegenerative disorders, fragile X-associated tremor/ataxia syndrome (FXTAS). Neurological signs of FXTAS, parkinsonism and rapid onset of cognitive decline have not been reported in individuals with an unmethylated full mutation (FM). Here, we report a Chilean family affected with FXS, inherited from a parent carrier of an FMR1 unmethylated full mosaic allele, who presented with a fast progressing FXTAS. This case suggests that the definition of FXTAS may need to be broadened to not only include those with a premutation but also those with an expanded allele in FM range with a lack of methylation leading to elevated FMR1-mRNA expression levels and subsequent RNA toxicity.
携带 FMR1 前突变等位基因（55-200 CGG 重复）的人常常会患上神经退行性疾病——脆性 X 相关震颤/共济失调综合征（FXTAS）。然而，在未甲基化的全突变（FM）个体中，尚未报道过 FXTAS 的神经体征、帕金森病和认知能力迅速下降。在这里，我们报告了一个智利的 FXS 家族，其遗传自一位 FMR1 未甲基化全嵌合体等位基因的携带者，该患者表现出快速进展的 FXTAS。该病例表明，FXTAS 的定义可能需要扩大，不仅包括那些具有前突变的患者，还包括那些在 FM 范围内扩展的等位基因，且缺乏甲基化导致 FMR1-mRNA 表达水平升高，进而导致 RNA 毒性的患者。
