在早产卵巢衰竭中使用SWS1-复合体:SWSAP1作为一种新的POI基因
Anna Lokchine1,2, Fang Zhang3,4, Laurence Cluzeau5
1Service de Cytogénétique et Biologie Cellulaire, CHU Rennes, Rennes, F-35000, France.
Human reproduction (Oxford, England)
|September 24, 2025
概括
这项研究发现了SWS1/ZSWIM7和SWSAP1中的新遗传变异,这对同源重组至关重要,导致过早的卵巢缺陷 (POI). 这些发现表明SWS1复合体与女性生育能力和生育过程的进展有关.
科学领域:
- 遗传学和生殖生物学
- 基因组医学是基因组医学.
- 分子遗传学 分子遗传学
背景情况:
- SWS1-复合体 (SWS1-SWSAP1-SPIDR) 对于小鼠的生育至关重要,淘汰模型显示中介性停止.
- 在SWS1/ZSWIM7和SPIDR的变体与早产卵巢缺陷 (POI) 有关,但SWSAP1变体以前在女性不孕症中未被描述.
研究的目的:
- 确定指SWIM域含有蛋白7 (SWS1/ZSWIM7) 和其参与过早卵巢缺陷 (POI) 的合作伙伴中的新型致病变体.
- 功能性地评估已识别的变异对同类间同类重组 (IH-HR) 和蛋白质稳定性的影响.
主要方法:
- 分析了被诊断为POI的五名法国患者的外基因组或基因组测序数据.
- 在模型中,使用小鼠胚胎干细胞进行了interhomolog同类重组 (IH-HR) 试验,并进行了西部斑分析.
- 功能验证侧重于SWS1/ZSWIM7中的两种新型变体和SWSAP1.1中的一种.
主要成果:
- 在五名患者中发现了五种不同的致病性或可能致病性变体,包括SWS1/ZSWIM7 (c.22del,c.151C>T) 的新型变体和SWSAP1 (c.353del) 的同胞性框架移位删除.
- 所有患者都呈现出严重的孤立POI,其特征是初级或早期的二次 amenorrhea和延迟的青春期.
- 在 silico 和 IH-HR 测试表明,已识别的 SWS1/ZSWIM7 和 SWSAP1 变异部分或完全损害了 IH-HR 活性并影响了蛋白质稳定性.
结论:
- 这项研究提供了第一个涉及SWSAP1在女性不孕症中的临床和功能证据,确定所有三个SWS1-复合体成员对女性生育能力至关重要.
- 这些发现突显了同类间同类重组 (IH-HR) 在介质进展中的作用及其在POI病变发生中的重要性.
- 需要进一步的研究来将SWSAP1变异与详细的表型相关联,并探索针对同源重组的治疗策略.
关键词:
在 SWSAP1 / SWS1/ZSWIM7 中,我们可以选择 SWSAP1 / SWS1/ZSWIM7.一个警察.舒 (shu) 综合体是一个复杂的建筑群.同类的重组组合.介质变化 (meiosis) 是一种变质的过程.过早的卵巢功能不充分.更多相关视频
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