The FMR1 gene contains a polymorphic CGG trinucleotide sequence within its 5′ untranslated region. More than 200 CGG repeats (termed a full mutation) underlie the severe neurodevelopmental condition fragile X syndrome, while repeat lengths that range between 55 and 200 (termed a premutation) result in the conditions fragile X-associated tremor/ataxia syndrome and fragile X-associated premature ovarian insufficiency (FXPOI). Premutations in FMR1 are the most common monogenic cause of premature ovarian insufficiency and are routinely tested for clinically; however, the mechanisms that contribute to the pathology are still largely unclear. As studies in this field move towards unravelling the molecular mechanisms involved in FXPOI aetiology, we review the evidence surrounding the two main theories which describe an RNA toxic gain-of-function mechanism, resulting in the loss of function of RNA-binding proteins, or a protein-based mechanism, where repeat-associated non-AUG translation leads to the formation of an abnormal polyglycine containing protein, called FMRpolyG.

中文翻译：

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脆弱的 X 相关性卵巢早衰的分子机制：它是基于 RNA 还是基于蛋白质？

的FMR1基因含有其5'非翻译区内的多态性CGG三核苷酸序列。超过 200 个 CGG 重复（称为完全突变）是严重神经发育状况脆性 X 综合征的基础，而重复长度介于 55 和 200（称为前突变）之间的重复长度导致脆性 X 相关震颤/共济失调综合征和脆性 X-相关的卵巢早衰（FXPOI）。FMR1 中的前置词是卵巢功能不全最常见的单基因原因，并在临床上进行常规检测；然而，导致病理学的机制在很大程度上仍不清楚。随着该领域的研究朝着解开 FXPOI 病因学中涉及的分子机制的方向发展，我们回顾了围绕两个主要理论的证据，这些理论描述了 RNA 毒性功能获得机制，导致 RNA 结合蛋白的功能丧失，或一种基于蛋白质的机制，其中与重复相关的非 AUG 翻译导致形成一种异常的含有多聚甘氨酸的蛋白质，称为 FMRpolyG。