{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T06:46:48Z","timestamp":1764226008777,"version":"3.41.2"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T00:00:00Z","timestamp":1730678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Follicle stimulating hormone (FSH) is a key pituitary gonadotropic hormone implicated in human fertility and is crucial for folliculogenesis and recruitment of new antral follicles. Variations in its receptor, FSHR, can lead to diverse reproductive phenotypes including ovarian hyperstimulation syndrome (OHSS) and premature ovarian insufficiency (POI). This study reports a novel case of FSHR\u2010related ovarian insufficiency in a patient with primary amenorrhea, subnormal AMH levels, and delayed puberty. Genetic exploration revealed two compound heterozygous intragenic deletions of FSHR. Specifically, the patient inherited a maternally derived deletion spanning exons 5\u201310 and a paternally derived deletion involving exons 3\u20136. Through chromosomal microarray analysis (CMA), exome sequencing, long\u2010range PCR, and Sanger sequencing, we characterized the breakpoints and confirmed the compound heterozygous deletions. The findings reveal a complete loss of function of both FSHR alleles, contributing to the patient's POI phenotype. This case emphasizes the complexity of genotype\u2013phenotype correlations in FSHR\u2010related disorders and the role of CNVs in POI phenotypes. Although these events are rare, our results advocate for the inclusion of CNV detection in the diagnostic workup of POI to ensure accurate diagnosis and better patient management.<\/jats:p>","DOI":"10.1002\/ajmg.a.63924","type":"journal-article","created":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T07:35:31Z","timestamp":1730792131000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification and Characterization of Novel <scp>FSHR<\/scp> Copy Number Variations Causing Premature Ovarian Insufficiency"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2236-7068","authenticated-orcid":false,"given":"Anna","family":"Lokchine","sequence":"first","affiliation":[{"name":"Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de Recherche en Sant\u00e9, Environnement et Travail)\u2013UMR_S1085  Rennes France"},{"name":"CHU Rennes, Service de Cytog\u00e9n\u00e9tique et Biologie Cellulaire  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Bergougnoux","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Mol\u00e9culaire et de Cytog\u00e9nomique, CHU de Montpellier  Montpellier France"},{"name":"PhyMedExp, Universit\u00e9 de Montpellier, INSERM U1046, CNRS UMR 9214  Montpellier France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nad\u00e8ge","family":"Servant","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Mol\u00e9culaire et de Cytog\u00e9nomique, CHU de Montpellier  Montpellier France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Akloul","sequence":"additional","affiliation":[{"name":"CHU Rennes, Service de G\u00e9n\u00e9tique Clinique, CLAD Ouest  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Launay","sequence":"additional","affiliation":[{"name":"CHU Rennes, Service de Cytog\u00e9n\u00e9tique et Biologie Cellulaire  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4981-3999","authenticated-orcid":false,"given":"Laura","family":"Mary","sequence":"additional","affiliation":[{"name":"CHU Rennes, Service de Cytog\u00e9n\u00e9tique et Biologie Cellulaire  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurence","family":"Cluzeau","sequence":"additional","affiliation":[{"name":"CHU Rennes, Service de Cytog\u00e9n\u00e9tique et Biologie Cellulaire  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathieu","family":"Philippe","sequence":"additional","affiliation":[{"name":"CHU Rennes, Service de Cytog\u00e9n\u00e9tique et Biologie Cellulaire  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathilde","family":"Domin\u2010Bernhard","sequence":"additional","affiliation":[{"name":"CHU Rennes, D\u00e9partement de Gyn\u00e9cologie Obst\u00e9trique et Reproduction Humaine  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sol\u00e8ne","family":"Duros","sequence":"additional","affiliation":[{"name":"CHU Rennes, D\u00e9partement de Gyn\u00e9cologie Obst\u00e9trique et Reproduction Humaine  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"Odent","sequence":"additional","affiliation":[{"name":"CHU Rennes, Service de G\u00e9n\u00e9tique Clinique, CLAD Ouest  Rennes France"},{"name":"Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes, IGDR UMR 6290 CNRS University of Rennes  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Tucker","sequence":"additional","affiliation":[{"name":"Reproductive Development Murdoch Children's Research Institute  Melbourne Victoria Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7oise","family":"Paris","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Mol\u00e9culaire et de Cytog\u00e9nomique, CHU de Montpellier  Montpellier France"},{"name":"Unit\u00e9 d'Endocrinologie et Gyn\u00e9cologie P\u00e9diatriques, Service de P\u00e9diatrie I H\u00f4pital A. de Villeneuve  Montpellier France"},{"name":"D\u00e9veloppement Embryonnaire, Fertilit\u00e9 et Environnement Universit\u00e9 de Montpellier, INSERM  Montpellier France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc\u2010Antoine","family":"Belaud\u2010Rotureau","sequence":"additional","affiliation":[{"name":"Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de Recherche en Sant\u00e9, Environnement et Travail)\u2013UMR_S1085  Rennes France"},{"name":"CHU Rennes, Service de Cytog\u00e9n\u00e9tique et Biologie Cellulaire  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"Jaillard","sequence":"additional","affiliation":[{"name":"Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de Recherche en Sant\u00e9, Environnement et Travail)\u2013UMR_S1085  Rennes France"},{"name":"CHU Rennes, Service de Cytog\u00e9n\u00e9tique et Biologie Cellulaire  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23626"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010genom\u2010110122"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092\u20108674(95)90275\u20109"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010021\u201001177\u2010y"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI3795"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dey389"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010019\u20100655\u20102"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2015.25"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00305"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920\u2010020\u201000787\u2010w"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815\u2010015\u20100595\u2010y"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/10935266221095305"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP\u201013\u20100351"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.11.005"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/det098"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2018.11.011"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016\u20101291"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13048\u2010016\u20100272\u20105"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.08.021"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1206643109"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015\u20101401"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2010.03.001"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.244"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1159\/000314958"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2017.09.010"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2008.8"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deu149"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222312735"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xfre.2020.08.008"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102018\u2010105778"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102012\u2010101351"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2022.111570"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew142"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2016\u20101047"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u201012\u2010391862\u20108.00002\u20108"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00707"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030065"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003358"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.13267"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp114"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.6065\/apem.2142116.058"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy261"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032\u2010019\u201000037\u20103"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63924","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T12:16:52Z","timestamp":1748348212000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63924"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,4]]},"references-count":43,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/ajmg.a.63924"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63924","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2024,11,4]]},"assertion":[{"value":"2024-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63924"}}