Evidence map›Paper›PMID 38252283›Full record

ArticleHuman genetics2024

Bi-allelic missense variants in MEI4 cause preimplantation embryonic arrest and female infertility.

Zhiqi Pan, Weijie Wang, Ling Wu, Zhongyuan Yao, Wenjing Wang, Yao Chen, Hao Gu, Jie Dong, Jian Mu, Zhihua Zhang and 7 more

Abstract read
PubMed Publisher
In one paragraph

Article in Human genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
13.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 12 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 7 institutions in 1 country.

Zhiqi Pan *Institute of Pediatrics, Children's Hospital of Fudan University, The Institutes of Biomedical Sciences, and the State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China.
Weijie Wang *Institute of Pediatrics, Children's Hospital of Fudan University, The Institutes of Biomedical Sciences, and the State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China.
Ling Wu *Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Zhongyuan Yao *The Reproductive Medical Center of Xiangya Hospital, Central South University, Changsha, 410008, China.
Wenjing Wang *Institute of Pediatrics, Children's Hospital of Fudan University, The Institutes of Biomedical Sciences, and the State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China.
Yao ChenObstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.
Hao GuInstitute of Pediatrics, Children's Hospital of Fudan University, The Institutes of Biomedical Sciences, and the State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China.
Jie DongInstitute of Pediatrics, Children's Hospital of Fudan University, The Institutes of Biomedical Sciences, and the State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China.
Jian MuInstitute of Pediatrics, Children's Hospital of Fudan University, The Institutes of Biomedical Sciences, and the State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China.
Zhihua ZhangInstitute of Pediatrics, Children's Hospital of Fudan University, The Institutes of Biomedical Sciences, and the State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China.
Jing FuShanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.
Qiaoli LiInstitute of Pediatrics, Children's Hospital of Fudan University, The Institutes of Biomedical Sciences, and the State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China.
Lei WangInstitute of Pediatrics, Children's Hospital of Fudan University, The Institutes of Biomedical Sciences, and the State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China.
Xiaoxi SunShanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.
Yanping KuangDepartment of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Qing SangInstitute of Pediatrics, Children's Hospital of Fudan University, The Institutes of Biomedical Sciences, and the State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China. sangqing@fudan.edu.cn.
Biaobang ChenNHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, 200032, China. chenbiaobang@163.com.
State Key Laboratory of Genetic EngineeringChildren's Hospital of Fudan University · CNFudan University · CNShanghai Ninth People's Hospital · CNObstetrics and Gynecology Hospital of Fudan University · CNShanghai Institute of Pharmaceutical Industry · CNXiangya Hospital Central South University · CN

Funding

China Postdoctoral Science Foundation 2021M700829National Key Research and Development Program for Young Scientists 2022YFC2702300National Key Research and Development Program of China 2021YFC2700100National Natural Science Foundation of China 81971382National Natural Science Foundation of China 82101939National Natural Science Foundation of China 82171643National Natural Science Foundation of China 82171644National Natural Science Foundation of China 82201829National Natural Science Foundation of China 82288102National Natural Science Foundation of China 82325021Project of the Shanghai Municipal Science and Technology Commission 21XD1420300
6 · The paper itself

Abstract

Preimplantation embryonic arrest is an important pathogenesis of female infertility, but little is known about the genetic factors behind this phenotype. MEI4 is an essential protein for DNA double-strand break formation during meiosis, and Mei4 knock-out female mice are viable but sterile, indicating that MEI4 plays a crucial role in reproduction. To date, MEI4 has not been found to be associated with any human reproductive diseases. Here, we identified six compound heterozygous and homozygous MEI4 variants-namely, c.293C > T, p.(Ser98Leu), c.401C > G, p.(Pro134Arg), c.391C > G, p.(Pro131Ala), c.914A > T, p.(Tyr305Phe), c.908C > G, p.(Ala303Gly), and c.899A > T, p.(Gln300Leu)-in four independent families that were responsible for female infertility mainly characterized by preimplantation embryonic arrest. In vitro, we found that these variants reduced the interaction between MEI4 and DNA. In vivo, we generated a knock-in mouse model and demonstrated that female mice were infertile and were characterized by developmental defects during oogenesis. Our findings reveal the important roles of MEI4 in human reproduction and provide a new diagnostic marker for genetic counseling of clinical infertility patients.

Indexed as

Cell Cycle ProteinsInfertility, FemaleMutation, MissenseAllelesAnimalsBlastocystFemaleHomeodomain ProteinsHumansMaleMeiosisMiceMice, KnockoutOogenesisPedigreeUbiquitin-Protein LigasesCcnb1ip1 protein, mouseCell Cycle ProteinsHomeodomain ProteinsMEI4 protein, humanUbiquitin-Protein Ligases

Identifiers

PMID38252283
OpenAlexW4391103774

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.