Case Report: A Novel Heterozygous ZP3 Deletion Associated With Empty Follicle Syndrome and Abnormal Follicular Development.
Case Report: A Novel Heterozygous ZP3 Deletion Associated With Empty Follicle Syndrome and Abnormal Follicular Development.
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与空卵泡综合征和卵泡发育异常相关的新型杂合 ZP3 缺失
DOI：
10.3389/fgene.2021.690070
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发表时间：
2021
影响因子：
3.7
通讯作者：
Dai C
中科院分区：
文献类型：
--
作者：
Chen Y;Wang Z;Wu Y;He W;Du J;Cai S;Gong F;Lu G;Lin G;Dai C
背景：空卵泡综合征（EFS）被定义为卵巢刺激后完全不能取卵。虽然ZP 1、ZP 2、ZP 3和LHCGR的几个突变已被确定为EFS的遗传原因，但其发病机制仍不清楚。方法：采用全外显子组测序（WES）技术对候选致病突变进行鉴定，并通过桑格测序进行验证。在CHO-K1细胞中进行研究以分析突变对蛋白质表达的影响。此外，免疫组织化学（IHC）染色用于检查EFS患者卵巢中的卵泡发育和透明带（ZP）组装。结果：在EFS患者中发现了一种新的ZP 3杂合缺失（c.565_579del[p.Thr189_Gly193del]）。它是显性遗传的，并导致ZP 3蛋白的显著降解。在次级卵泡中观察到胞质变性的卵母细胞和异常的ZP组装，并存在许多空卵泡样结构。结论：我们发现了一个新的ZP 3突变，扩大了与人类EFS相关的突变谱。我们还显示了与杂合子ZP 3突变的EFS患者的异常卵泡发育和ZP组装，这为EFS的发病机制提供了新的见解。
Background: Empty follicle syndrome (EFS) is defined as the complete failure to retrieve oocytes after ovarian stimulation. Although several mutations in ZP1, ZP2, ZP3, and LHCGR have been identified as genetic causes of EFS, its pathogenesis is still not well-understood. Methods: Whole-exome sequencing (WES) was employed to identify the candidate pathogenic mutations, which were then verified by Sanger sequencing. A study in CHO-K1 cells was performed to analyze the effect of the mutation on protein expression. Additionally, immunohistochemistry (IHC) staining was used to examine follicular development and zona pellucida (ZP) assembly in the ovary of an EFS patient. Results: A novel heterozygous deletion in ZP3 (c.565_579del[p.Thr189_Gly193del]) was identified in the EFS patient. It was inherited dominantly and resulted in significant degradation of the ZP3 protein. Oocytes with degenerated cytoplasm and abnormal ZP assembly were observed in follicles up to the secondary stage, and many empty follicle-like structures were present. Conclusion: We identified a novel ZP3 mutation that expands the mutational spectrum associated with human EFS. We also showed the abnormal follicular development and ZP assembly of the EFS patient with the heterozygous ZP3 mutation, which provides new insights into the pathogenesis of EFS.
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影响因子：
6.1
作者：
Dai, Can;Chen, Yongzhe;Lin, Ge
通讯作者：
Lin, Ge
影响因子：
21.3
作者：
Jovine, L;Qi, HY;Wassarman, PM
通讯作者：
Wassarman, PM
ZP3 的新突变导致空卵泡综合征和透明带形成异常
影响因子：
3.1
作者：
Zhang, Dazhi;Zhu, Lixia;Zhang, Xianqin
通讯作者：
Zhang, Xianqin
影响因子：
6.1
作者：
Awonuga, A;Govindbhai, J;Schnauffer, K
通讯作者：
Schnauffer, K
影响因子：
15.8
作者：
Mascarenhas MN;Flaxman SR;Boerma T;Vanderpoel S;Stevens GA
通讯作者：
Stevens GA