鉴定新型化合物异质合体ZFP36L2变体,涉及卵细胞成熟缺陷和女性不孕症
Xian Wan1,2, Huiling Hu3, Jiaqi Sun4
1The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
Journal of assisted reproduction and genetics
|June 3, 2024
概括
新的ZFP36L2变种通过破坏mRNA降解,导致卵细胞成熟缺陷. 这项研究揭示了人类卵细胞转录组的变化,有助于为女性不孕症提供遗传咨询.
科学领域:
- 生殖生物学 生殖生物学
- 分子遗传学 分子遗传学
- 人类遗传学 人类遗传学
背景情况:
- 卵细胞成熟对于女性生育能力至关重要.
- 卵细胞成熟的缺陷可能导致不孕.
- 尚不完全了解ZFP36L2在卵细胞发育中的作用.
研究的目的:
- 为了研究卵细胞成熟缺陷的致病性.
- 识别与受损卵细胞成熟相关的遗传变异.
- 描述这些缺陷背后的分子机制.
主要方法:
- 整体外基因组测序和桑格测序用于变种识别.
- 在体外功能测试 (HeLa细胞中的过渡性转染) 用于变体表征.
- 实时RT-PCR和单细胞RNA测序以评估卵细胞中的mRNA代谢.
主要成果:
- 在患有卵细胞成熟缺陷的患者中鉴定了ZFP36L2 (c.186T>G,p.His62Gln和c.869C>T,p.Pro290Leu) 的新型组合异构体变异.
- 这些ZFP36L2变种危害ZFP36L2-CONT6L复合结合并损害mRNA降解.
- 由于ZFP36L2变种,与细胞分裂,线粒体功能和核糖体代谢相关的人类卵细胞转录组改变的特征.
结论:
- 扩大了ZFP36L2.2.的已知突变谱.
- 关于与ZFP36L2变异相关的人类卵细胞转录组变异的第一份报告.
- 这些发现为关于与ZFP36L2.2相关的女性不孕症的遗传咨询提供了基础.
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