TY - JOUR T1 - Biallelic variants in <em>ZFP36L2</em> cause female infertility characterised by recurrent preimplantation embryo arrest JF - Journal of Medical Genetics JO - J Med Genet DO - 10.1136/jmedgenet-2021-107933 SP - jmedgenet-2021-107933 AU - Wei Zheng AU - Qian-Qian Sha AU - Huiling Hu AU - Fei Meng AU - Qinwei Zhou AU - Xueqin Chen AU - Shuoping Zhang AU - Yifan Gu AU - Xian Yan AU - Lei Zhao AU - Yurong Zong AU - Liang Hu AU - Fei Gong AU - Guangxiu Lu AU - Heng-Yu Fan AU - Ge Lin Y1 - 2021/10/05 UR - http://jmg.bmj.com/content/early/2021/10/05/jmedgenet-2021-107933.abstract N2 - 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.Data are available upon reasonable request. ER -