Fragile X and fragile X-associated tremor-ataxia syndrome (FXTAS) are caused by mutations of the FMR1 gene. The mutations causing FXTAS can expand in a generation to a "full mutation" causing fragile X syndrome. The mutations causing FXTAS and the phenotype, fragile X-associated premature ovarian insufficiency (FXPOI), are referred to as the FMR1 premutation (PM). The objective of this paper was to formulate a theory to explain the Mechanism for FXPOI.Recent research on fragile X syndrome and FXTAS has led to sophisticated theories about the mechanisms underlying these diseases. It has been proposed that similar mechanisms underlie FXPOI. Utilizing recent research on FXTAS, but a more detailed application of ovarian physiology, we present a more ovarian specific theory as to the primary mechanism explaining the development of FXPOI.The FXPOI phenotype may best be viewed as derivative of the observation that fragile X PM carriers experience menopause an average of 5 years earlier than non-carriers. Women carrying the PM experience an earlier menopause because of an accelerated activation of their primordial follicle pool. This acceleration of primordial follicle activation occurs, in part, because of diminished AMH production. AMH production is diminished because of accelerated atresia of early antral follicles. This accelerated atresia likely occurs because the fragile X PM leads to a slowing of the rate of granulosa cell mitosis in some follicles.

中文翻译：

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解释脆性 X 相关卵巢早衰的机制。

脆性 X 细胞和脆性 X 细胞相关震颤共济失调综合征 (FXTAS) 是由 FMR1 基因突变引起的。导致 FXTAS 的突变可以在一代人中扩展为导致脆性 X 综合征的“完全突变”。导致 FXTAS 和表型脆性 X 相关卵巢早衰 (FXPOI) 的突变被称为 FMR1 前突变 (PM)。本文的目的是建立一个理论来解释 FXPOI 的机制。最近对脆性 X 综合征和 FXTAS 的研究已经产生了关于这些疾病的机制的复杂理论。有人提出 FXPOI 背后也有类似的机制。利用最近对 FXTAS 的研究，但更详细地应用卵巢生理学，我们提出了一种更具体的卵巢特定理论，以解释 FXPOI 发展的主要机制。FXPOI 表型最好被视为脆弱的 X PM 携带者观察的衍生结果比非携带者平均早 5 年进入更年期。携带 PM 的女性由于原始卵泡池的加速激活而经历更年期。原始卵泡激活加速的部分原因是 AMH 产生减少。由于早期窦状卵泡加速闭锁，AMH 的产生减少。这种加速闭锁的发生可能是因为脆弱的 X PM 导致某些卵泡中颗粒细胞有丝分裂速度减慢。