Biallelic variants in ZFP36L2 cause female infertility characterised by recurrent preimplantation embryo arrest

被引：22

作者：

Zheng, Wei ^{[1
,2
]}

Sha, Qian-Qian ^{[3
]}

Hu, Huiling ^{[2
]}

Meng, Fei ^{[1
]}

Zhou, Qinwei ^{[1
]}

Chen, Xueqin ^{[2
]}

Zhang, Shuoping ^{[1
]}

Gu, Yifan ^{[1
,2
]}

Yan, Xian ^{[1
]}

Zhao, Lei ^{[1
]}

Zong, Yurong ^{[1
]}

Hu, Liang ^{[1
,2
]}

Gong, Fei ^{[1
,2
]}

Lu, Guangxiu ^{[1
,2
]}

Fan, Heng-Yu ^{[4
]}

Lin, Ge ^{[1
,2
]}

机构：

[1] Reprod & Genet Hosp CITIC XIANGYA, Clin Res Ctr Reprod & Genet Hunan Prov, Changsha, Hunan, Peoples R China

[2] Cent South Univ, NHC Key Lab Human Stem & Reprod Engn, Lab Reprod & Stem Cell Engn, Changsha, Hunan, Peoples R China

[3] Guangdong Second Prov Gen Hosp, Reprod Med Ctr, Fertil Preservat Lab, Guangzhou, Guangdong, Peoples R China

[4] Zhejiang Univ, Life Sci Inst, Hangzhou, Zhejiang, Peoples R China

来源：

JOURNAL OF MEDICAL GENETICS | 2022年 / 59卷 / 09期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

reproductive medicine; human genetics; MESSENGER-RNA DECAY; CYTOPLASMIC MATURATION; POLYMERASE-II; HUMAN OOCYTE; MUTATIONS; ACTIVATION; PROTEINS; NUCLEAR; TUBB8; RICH;

D O I：

10.1136/jmedgenet-2021-107933

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background Recurrent preimplantation embryo developmental arrest (RPEA) is the most common cause of assisted reproductive technology treatment failure associated with identified genetic abnormalities. Variants in known maternal genes can only account for 20%-30% of these cases. The underlying genetic causes for the other affected individuals remain unknown. Methods Whole exome sequencing was performed for 100 independent infertile females that experienced RPEA. Functional characterisations of the identified candidate disease-causative variants were validated by Sanger sequencing, bioinformatics and in vitro functional analyses, and single-cell RNA sequencing of zygotes. Results Biallelic variants in ZFP36L2 were associated with RPEA and the recurrent variant (p.Ser308_Ser310del) prevented maternal mRNA decay in zygotes and HeLa cells. Conclusion These findings emphasise the relevance of the relationship between maternal mRNA decay and human preimplantation embryo development and highlight a novel gene potentially responsible for RPEA, which may facilitate genetic diagnoses.

引用

页码：850 / 857

页数：8

共 45 条

[31] CNOT6L couples the selective degradation of maternal transcripts to meiotic cell cycle progression in mouse oocyte [J].