Premature ovarian insufficiency (POI) is the cessation of menstruation before the age of 40 and can result from different etiologies, including genetic, autoimmune, and iatrogenic. Of the genetic causes, single-gene mutations and cytogenetic alterations, such as X-chromosome aneuploidies and chromosome rearrangements, can be associated with POI. In this review, we summarize the genetic factors linked to POI and list the main candidate genes. We discuss the association of these genes with the ovarian development, the functional consequences of different mutational mechanisms and biological processes that are frequently disrupted during POI pathogenesis. Additionally, we focus on the high prevalence of X-autosome translocations involving the critical regions in Xq, known as POI1 and POI2, and ddiscuss in depth the main hypotheses proposed to explain this association. Although the incorrect pairing of chromosomes during meiosis could lead to oocyte apoptosis, the reason for the prevalence of X-chromosome breakpoints at specific regions remains unclear. In most cases, studies on genes disrupted by balanced structural rearrangements cannot explain the ovarian failure. Thus, the position effect has emerged as a putative explanation for genetic mechanisms as translocations possibly result in changes in overall chromatin topology due to chromosome repositioning. Given the tremendous impact of POI on women's quality of life, we highlight the value of investigations in to the interplay between ovarian function and gene regulation to deepen our understanding of the molecular mechanisms related to this disease, with the ultimate goal of improving patients' care and assistance.

中文翻译：

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卵巢早衰的遗传学及其与 X 常染色体易位的关系

卵巢早衰 (POI) 是指在 40 岁之前停止月经，可由多种病因引起，包括遗传、自身免疫和医源性。在遗传原因中，单基因突变和细胞遗传学改变，如 X 染色体非整倍体和染色体重排，可能与 POI 相关。在这篇综述中，我们总结了与 POI 相关的遗传因素并列出了主要的候选基因。我们讨论了这些基因与卵巢发育的关联、不同突变机制的功能后果以及在 POI 发病过程中经常被破坏的生物学过程。此外，我们关注涉及 Xq 关键区域（称为 POI1 和 POI2）的 X 常染色体易位的高流行率，并深入讨论为解释这种关联而提出的主要假设。尽管减数分裂过程中染色体的错误配对可能导致卵母细胞凋亡，但特定区域 X 染色体断点普遍存在的原因仍不清楚。在大多数情况下，对平衡结构重排破坏的基因的研究无法解释卵巢功能衰竭。因此，位置效应已成为遗传机制的推定解释，因为易位可能导致染色体重新定位导致整体染色质拓扑结构的变化。鉴于 POI 对女性生活质量的巨大影响，我们强调了调查卵巢功能和基因调控之间相互作用的价值，以加深我们对与这种疾病相关的分子机制的理解，