新型PATL2变种导致女性不育,卵细胞成熟缺陷
Hua-Ying Hu1, Ge-Han Zhang2, Wei-Fen Deng3
1Birth Defects Prevention and Control Technology Research Center, Medical Innovation Research Division of Chinese, PLA General Hospital, Beijing, 100853, China.
Journal of assisted reproduction and genetics
|July 2, 2024
概括
新的PATL2基因突变导致卵细胞成熟缺陷 (OOMD),导致体外受精失败. 这项研究确定了新的突变及其对卵细胞发育的影响,有助于基因咨询和OOMD诊断.
科学领域:
- 遗传学 遗传学 是一个
- 生殖生物学 生殖生物学
- 分子生物学分子生物学
背景情况:
- 卵细胞成熟缺陷 (OOMD) 是体外受精 (IVF) 失败的一个罕见原因.
- OOMD的特点是产生不成熟的卵细胞.
- PATL2基因突变与不同发育阶段的卵细胞停产有关.
研究的目的:
- 在三个案例中调查OOMD的遗传基础.
- 为了识别和描述PATL2基因中的新突变.
- 了解这些突变对卵细胞成熟的功能影响.
主要方法:
- 招募了三个OOMD案件.
- 综合的多平台实验室调查,包括整个外基因组测序 (WES).
- 在 silico 病原性预测,分子动态分析和细胞转染实验.
主要成果:
- 在PATL2中发现了四种诊断变异,包括两个新突变:c.709C>T (p.R237*) 和c.1486_1487delinsT (p.A496Sfs*4).
- 在分析预测了变体的有害影响,分子动态显示蛋白质结构和稳定性的破坏.
- 传染实验表明,PATL2变体的蛋白质大小和表达水平发生变化,以及关键发育基因的放松调节.
结论:
- 确定的PATL2变异 (p.R237*和p.A496Sfs*4) 影响蛋白质特征和基因表达,这对卵细胞成熟和胚胎发育至关重要.
- 这些发现扩大了与OOMD相关的PATL2变异的已知光谱.
- 这项研究为受影响家庭的遗传咨询提供了证据,并支持PATL2分析用于OOMD诊断.
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