Fragile X syndrome (FXS) is caused by a full mutation of the FMR1 gene (>200 CGG repeats and subsequent methylation), such that there is little or no FMR1 protein (FMRP) produced, leading to intellectual disability (ID). Individuals with the premutation allele (55–200 CGG repeats, generally unmethylated) have elevated FMR1 mRNA levels, a consequence of enhanced transcription, resulting in neuronal toxicity and a spectrum of premutation-associated disorders, including the neurodegenerative disorder fragile X-associated tremor/ataxia syndrome (FXTAS). Here we described 14 patients who had both lowered FMRP and elevated FMR1 mRNA levels, representing dual mechanisms of clinical involvement, which may combine features of both FXS and FXTAS. In addition, the majority of these cases show psychiatric symptoms, including bipolar disorder, and/or psychotic features, which are rarely seen in those with just FXS.

脆性 X 综合征 (FXS) 是由FMR1基因的完全突变（>200 个 CGG 重复和随后的甲基化）引起的，因此几乎没有或没有FMR1蛋白 (FMRP) 产生，导致智力残疾 (ID)。具有前突变等位基因（55-200 个 CGG 重复，通常未甲基化）的个体FMR1 mRNA 水平升高，这是转录增强的结果，导致神经元毒性和一系列前突变相关疾病，包括神经退行性疾病脆性 X 相关震颤/共济失调综合征（FXTAS）。在这里，我们描述了 14 名 FMRP 降低和FMR1升高的患者mRNA 水平，代表临床参与的双重机制，可能结合了 FXS 和 FXTAS 的特征。此外，这些病例中的大多数表现出精神症状，包括双相情感障碍和/或精神病特征，这在仅有 FXS 的患者中很少见。