{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:35:09Z","timestamp":1790660109142,"version":"4.1.0"},"reference-count":67,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2022YFC2703800"],"award-info":[{"award-number":["2022YFC2703800"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32288101,82125014"],"award-info":[{"award-number":["32288101,82125014"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2021-I2M-5-001"],"award-info":[{"award-number":["2021-I2M-5-001"]}]},{"DOI":"10.13039\/100020732","name":"Innovative Research Team of High-Level Local Universities in Shanghai","doi-asserted-by":"crossref","award":["SHSMU-ZLCX20210200"],"award-info":[{"award-number":["SHSMU-ZLCX20210200"]}],"id":[{"id":"10.13039\/100020732","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Clinical Research Program of Nanfang Hospital, Southern Medical University","award":["2018CR016"],"award-info":[{"award-number":["2018CR016"]}]},{"name":"Strategic Collaborative Research Program of the Ferring Institute of Reproductive Medicine","award":["FIRMC200502"],"award-info":[{"award-number":["FIRMC200502"]}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"crossref","award":["U54HG003079"],"award-info":[{"award-number":["U54HG003079"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,15]]},"abstract":"<jats:p>\n                    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 (\n                    <jats:italic>MGA<\/jats:italic>\n                    ) were significantly enriched in the discovery cohort, accounting for 2.6% of POI cases, while no\n                    <jats:italic>MGA<\/jats:italic>\n                    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\n                    <jats:italic>MGA<\/jats:italic>\n                    LoF variants in 1.0%, 1.4%, 1.0%, and 1.0% of POI cases, respectively. Overall, a total of 37 distinct heterozygous\n                    <jats:italic>MGA<\/jats:italic>\n                    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,\n                    <jats:italic>\n                      Mga\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1172\/jci183758","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T14:00:36Z","timestamp":1731592836000},"source":"Crossref","is-referenced-by-count":5,"title":["MGA loss-of-function variants cause premature ovarian insufficiency"],"prefix":"10.1172","volume":"134","author":[{"given":"Shuyan","family":"Tang","sequence":"first","affiliation":[{"name":"Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6354-238X","authenticated-orcid":true,"given":"Ting","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Song","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingbo","family":"Wang","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China."},{"name":"Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar","family":"Rajkovic","sequence":"additional","affiliation":[{"name":"Department of Pathology, Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqi","family":"Lin","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiling","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujun","family":"Liu","sequence":"additional","affiliation":[{"name":"Human Phenome Institute, Zhangjiang Fudan International Innovation Center and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Tian","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangguo","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhui","family":"Lai","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhua","family":"Xu","sequence":"additional","affiliation":[{"name":"Human Phenome Institute, Zhangjiang Fudan International Innovation Center and"},{"name":"School of Life Sciences, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9201-2321","authenticated-orcid":true,"given":"Li","family":"Jin","sequence":"additional","affiliation":[{"name":"Human Phenome Institute, Zhangjiang Fudan International Innovation Center and"},{"name":"School of Life Sciences, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanni","family":"Ke","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China."},{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4722-1575","authenticated-orcid":true,"given":"Shidou","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Qin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Medical Genetics and Genomics, Fudan University, Shanghai, China."},{"name":"Human Phenome Institute, Zhangjiang Fudan International Innovation Center and"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases, Soong Ching Ling Institute of Maternity and Child Health, International Peace Maternity and Child Health Hospital of China Welfare Institute, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6637-6631","authenticated-orcid":true,"given":"Zi-Jiang","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, China."},{"name":"Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China."},{"name":"Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (no. 2021RU001), Jinan, China."},{"name":"Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,11,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000451757.51964.98"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1080\/13697137.2019.1574738"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp2116488"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1080\/13697137.2022.2153033"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-2115(97)00085-7"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/13.7.1796"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-09-0231"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deab192"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab775"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104246"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02194-3"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-024-01351-1"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-023-01104-6"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nature08494"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0177-4"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908753"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.6500"},{"issue":"1","key":"B18","first-page":"128","article-title":"Translation repression by maternal RNA binding protein Zar1 is essential for early oogenesis in zebrafish","volume":"144","author":"Miao","year":"2017","journal-title":"Development"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2021.07.013"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110017"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-0322-9"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06595-3"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03205-y"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz829"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23626"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1242\/dev.111104"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe5689"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1177061"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.03.007"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.10.029"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2005570117"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab163"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007193"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.21064"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31759-6"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1172\/JCI162315"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33323-8"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2023.03.013"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02405-5"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005419"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.2040"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-021-02083-7"},{"issue":"2","key":"B44","first-page":"576","article-title":"MCM8 and MCM9 nucleotide variants in women with primary ovarian insufficiency","volume":"102","author":"Desai","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2007.02.032"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq559"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14288-y"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-023-2408-2"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42695-4"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1268"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioaa012"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.042"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.085"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.034"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0170555"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01767-y"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00532-9"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-023-2360-3"},{"issue":"3","key":"B67","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation (Camb)"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/183758\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T23:00:09Z","timestamp":1779231609000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/183758"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,15]]},"references-count":67,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11,15]]},"published-print":{"date-parts":[[2024,11,15]]}},"alternative-id":["10.1172\/JCI183758"],"URL":"https:\/\/doi.org\/10.1172\/jci183758","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,15]]},"article-number":"e183758"}}