Evidence map›Paper›PMID 39545409›Full record

ArticleThe Journal of clinical investigation2024

MGA loss-of-function variants cause premature ovarian insufficiency.

Shuyan Tang, Ting Guo, Chengcheng Song, Lingbo Wang, Jun Zhang, Aleksandar Rajkovic, Xiaoqi Lin, Shiling Chen, Yujun Liu, Weidong Tian and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
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

23 authors.

Shuyan TangObstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China.
Ting GuoState Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, China.
Chengcheng SongObstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China.
Lingbo WangObstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China.
Jun ZhangCenter for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Aleksandar RajkovicDepartment of Pathology, Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California, USA.
Xiaoqi LinObstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China.
Shiling ChenCenter for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Yujun LiuHuman Phenome Institute, Zhangjiang Fudan International Innovation Center and.
Weidong TianSchool of Life Sciences, Fudan University, Shanghai, China.
Bangguo WuShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China.
Shixuan WangDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Wenwen WangDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yunhui LaiCenter for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Ao WangCenter for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Shuhua XuHuman Phenome Institute, Zhangjiang Fudan International Innovation Center and.
Li JinHuman Phenome Institute, Zhangjiang Fudan International Innovation Center and.
Hanni KeObstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China.
Shidou ZhaoState Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, China.
Yan LiDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yingying QinState Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, China.
Feng ZhangObstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China.
Zi-Jiang ChenState Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, China.

Funding

Large Scale Genome SequencingU54HG003079 · NHGRI · WASHINGTON UNIVERSITY · PI DUTCHER, SUSAN K · 2004 to 2016
$445.7M
NHGRI NIH HHS U54 HG003079
6 · The paper itself

Abstract

Although premature ovarian insufficiency (POI), a common cause of female infertility and subfertility, has a well-established hereditary component, the genetic factors currently implicated in POI account for only a limited proportion of cases. Here, using an exome-wide, gene-based case-control analysis in a discovery cohort comprising 1,027 POI cases and 2,733 ethnically matched women controls from China, we found that heterozygous loss-of-function (LoF) variants of MAX dimerization protein (MGA) were significantly enriched in the discovery cohort, accounting for 2.6% of POI cases, while no MGA LoF variants were found in the matched control females. Further exome screening was conducted in 4 additional POI cohorts (2 from China and 2 from the United States) for replication studies, and we identified heterozygous MGA LoF variants in 1.0%, 1.4%, 1.0%, and 1.0% of POI cases, respectively. Overall, a total of 37 distinct heterozygous MGA LoF variants were discovered in 38 POI cases, accounting for approximately 2.0% of the total 1,910 POI cases analyzed in this study. Accordingly, Mga+/- female mice were subfertile, exhibiting shorter reproductive lifespan and decreased follicle number compared with WT, mimicking the observed phenotype in humans. Our findings highlight the essential role of MGA deficiency for impaired female reproductive ability.

Indexed as

Loss of Function MutationPrimary Ovarian InsufficiencyAdultAnimalsCase-Control StudiesFemaleHeterozygoteHumansMiceGenetic diseasesGeneticsMonogenic diseasesReproductive biology

Identifiers

PMID39545409
PMCPMC11563689

What OpenQuestion holds

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Registered trials

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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.