{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:52:45Z","timestamp":1790801565987,"version":"4.1.0"},"reference-count":87,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>While variants in hundreds of genes have been linked to premature ovarian insufficiency (POI), monogenic disorders account for fewer than half of idiopathic POI cases in adolescents with 46,XX karyotype. This highlights the need for the further genetic investigation across diverse populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>\n                      We recruited 63 Russian patients diagnosed with 46,XX POI before age 18. All underwent\n                      <jats:italic>FMR1<\/jats:italic>\n                      premutation testing and whole-exome sequencing (WES). Copy number variation (CNV) analysis was conducted on WES data. Segregation studies by Sanger sequencing were performed where samples from the patients\u2019 relatives were available.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified variants in 15 genes in 38% of the cohort, including 13 causative genes (\n                      <jats:italic>FMR1<\/jats:italic>\n                      ,\n                      <jats:italic>DCAF17, FOXL2, STAG3, TP63, BNC1, CPEB1, NOBOX, LMNA, FSHR, SPIDR, MCM8, EIF2B2<\/jats:italic>\n                      ) and 2 candidate genes (\n                      <jats:italic>MYRF, LATS1<\/jats:italic>\n                      ). 3.2% of patients carried an\n                      <jats:italic>FMR1<\/jats:italic>\n                      premutation. WES detected causative single nucleotide variants (SNVs) in 15 patients (17.5% of the cohort). CNV analysis increased the diagnostic yield to 20.6%, identifying 15q25.2 microdeletions (\n                      <jats:italic>BNC1<\/jats:italic>\n                      ,\n                      <jats:italic>CPEB1<\/jats:italic>\n                      ) in two patients and\n                      <jats:italic>FSHR<\/jats:italic>\n                      exon 2 deletion in one patient with resistant ovary syndrome. Overall, the combination of molecular genetic approaches established a diagnosis of monogenic POI (pathogenic or likely pathogenic variants) in 23.8% of adolescents with normal female karyotype. 5 patients (7.9%) carried variants of unknown significance in\n                      <jats:italic>FSHR<\/jats:italic>\n                      ,\n                      <jats:italic>LMNA<\/jats:italic>\n                      ,\n                      <jats:italic>NOBOX<\/jats:italic>\n                      ,\n                      <jats:italic>SPIDR, LATS1<\/jats:italic>\n                      genes, warranting further investigation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Our findings demonstrate that WES is an effective diagnostic tool for adolescents with POI and should supplement standard karyotyping and\n                      <jats:italic>FMR1<\/jats:italic>\n                      testing in routine clinical practice. We report several novel variants in POI-associated genes and propose new gene-disease association.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1687148","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T05:13:09Z","timestamp":1764220389000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Novel variants associated with premature ovarian insufficiency in Russian adolescents"],"prefix":"10.3389","volume":"16","author":[{"given":"Polina","family":"Tsabai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaira","family":"Kumykova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Averkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadezhda","family":"Pavlova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Maslennikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bolshakova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zalina","family":"Batyrova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Kolpakova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Bystritskiy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Karetnikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Ekimov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Goltsov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kuznetsova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Turchinets","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Mukosey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taisiya","family":"Kochetkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Sadelov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jekaterina","family":"Shubina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Uvarova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Yureneva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Trofimov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennady","family":"Sukhikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1080\/13697137.2019.1574738","article-title":"The global prevalence of primary ovarian insufficiency and early menopause: a meta-analysis","volume":"22","author":"Golezar","year":"2019","journal-title":"Climacteric"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hoae065","article-title":"Evidence-based guideline: premature ovarian insufficiency","author":"Panay","year":"2024","journal-title":"Hum Reprod Open"},{"key":"B3","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/s13048-025-01714-2","article-title":"The risk factors, pathogenesis and treatment of premature ovarian insufficiency","volume":"18","author":"Huang","year":"2025","journal-title":"J Ovarian Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1464803","article-title":"Primary ovarian insufficiency: update on clinical and genetic findings","volume":"15","author":"Federici","year":"2024","journal-title":"Front Endocrinol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dead066","article-title":"Association of genetic disorders and congenital malformations with premature ovarian insufficiency: a nationwide register-based study","volume":"38","author":"Silv\u00e9n","year":"2023","journal-title":"Hum Reprod"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jadohealth.2019.11.315","article-title":"Primary ovarian insufficiency nationwide incidence rate and etiology among Israeli adolescents","volume":"66","author":"Gruber","year":"2020","journal-title":"J Adolesc Health"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deac014","article-title":"Incidence and familial risk of premature ovarian insufficiency in the Finnish female population","volume":"37","author":"Silv\u00e9n","year":"2022","journal-title":"Hum Reprod"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2018.03.010","article-title":"Advances in the molecular pathophysiology, genetics, and treatment of primary ovarian insufficiency","volume":"29","author":"Huhtaniemi","year":"2018","journal-title":"Trends Endocrinol Metab TEM"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02194-3","article-title":"Landscape of pathogenic mutations in premature ovarian insufficiency","volume":"29","author":"Ke","year":"2023","journal-title":"Nat Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104246","article-title":"Genetic landscape of a large cohort of Primary Ovarian Insufficiency: New genes and pathways and implications for personalized medicine","volume":"84","author":"Heddar","year":"2022","journal-title":"EBioMedicine"},{"key":"B11","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/j.tem.2018.07.002","article-title":"Molecular genetics of premature ovarian insufficiency","volume":"29","author":"Jiao","year":"2018","journal-title":"Trends Endocrinol Metab TEM"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics15131724","article-title":"Changing etiological spectrum of premature ovarian insufficiency over the past decades: A comparative analysis of two cohorts from a single center","volume":"15","author":"Csehely","year":"2025","journal-title":"Diagnostics"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dead180","article-title":"Association between ovarian reserve and spontaneous miscarriage and their shared genetic architecture","volume":"38","author":"Yi","year":"2023","journal-title":"Hum Reprod"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-023-02761-8","article-title":"Novel deleterious splicing variant in HFM1 causes gametogenesis defect and recurrent implantation failure: concerning the risk of chromosomal abnormalities in embryos","volume":"40","author":"Tang","year":"2023","journal-title":"J Assist Reprod Genet"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-025-03663-7","article-title":"Genetic variants in diminished ovarian reserve and premature ovarian insufficiency: implications for assisted reproductive outcomes","author":"Xu","year":"2025","journal-title":"J Assist Reprod Genet"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaf124","article-title":"A tiered approach to exome sequencing analysis in early-onset primary ovarian insufficiency","volume":"110","author":"McGlacken-Byrne","year":"2025","journal-title":"J Clin Endocrinol Metab"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/life15091366","article-title":"An evidence-based approach to the management of primary ovarian insufficiency in adolescents and young women","volume":"15","author":"Bakhsh","year":"2025","journal-title":"Life"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0686-8","article-title":"Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)","volume":"22","author":"Riggs","year":"2020","journal-title":"Genet Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2010.07.1069","article-title":"Age-specific nomogram for the decline in antral follicle count throughout the reproductive period","volume":"95","author":"La Marca","year":"2011","journal-title":"Fertil Steril"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2019-00248","article-title":"Exome sequencing of a primary ovarian insufficiency cohort reveals common molecular etiologies for a spectrum of disease","volume":"104","author":"Jolly","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deab192","article-title":"Targeted whole exome sequencing and Drosophila modelling to unveil the molecular basis of primary ovarian insufficiency","volume":"36","author":"Bestetti","year":"2021","journal-title":"Hum Reprod"},{"key":"B23","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s10815-018-1349-4","article-title":"Gene variants identified by whole-exome sequencing in 33 French women with premature ovarian insufficiency","volume":"36","author":"Yang","year":"2019","journal-title":"J Assist Reprod Genet"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3390\/genes16030251","article-title":"Genetics investigation of idiopathic premature ovarian insufficiency: contribution of array-CGH and next-generation sequencing","volume":"16","author":"Cozette","year":"2025","journal-title":"Genes"},{"key":"B25","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s12958-024-01227-5","article-title":"FMR1 allelic complexity in premutation carriers provides no evidence for a correlation with age at amenorrhea","volume":"22","author":"Rodrigues","year":"2024","journal-title":"Reprod Biol Endocrinol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1196\/annals.1429.029","article-title":"Reproductive health of adolescent girls\u00a0who carry the FMR1 premutation: expected phenotype based on current knowledge of fragile X\u2013associated primary ovarian insufficiency","volume":"1135","author":"De Caro","year":"2008","journal-title":"Ann N Y Acad Sci"},{"key":"B27","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s13048-023-01104-6","article-title":"Next-generation sequencing of 500 POI patients identified novel responsible monogenic and oligogenic variants","volume":"16","author":"Luo","year":"2023","journal-title":"J\u00a0Ovarian Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02405-5","article-title":"Penetrance of pathogenic genetic variants associated with premature ovarian insufficiency","volume":"29","author":"Shekari","year":"2023","journal-title":"Nat Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2023.11.033","article-title":"New insights on mitochondrial heteroplasmy observed in ovarian diseases","volume":"65","author":"Zhou","year":"2024","journal-title":"J Adv Res"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2025.2528563","article-title":"Mechanism of crosstalk between DNA methylation and histone acetylation and related advances in diagnosis and treatment of premature ovarian failure","volume":"20","author":"Li","year":"2025","journal-title":"Epigenetics"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.11.006","article-title":"Why are some patients with 45,X Turner syndrome fertile? A young girl with classical 45,X Turner syndrome and a cryptic mosaicism in the ovary","volume":"115","author":"Nadesapillai","year":"2021","journal-title":"Fertil Steril"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2021.12.023","article-title":"Whole exome sequencing in a cohort of familial premature ovarian insufficiency cases reveals a broad array of pathogenic or likely pathogenic variants in 50% of families","volume":"117","author":"Rouen","year":"2022","journal-title":"Fertil Steril"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62501","article-title":"Expanding on the phenotypic spectrum of Woodhouse-Sakati syndrome due to founder pathogenic variant in DCAF17 : Report of 58 additional patients from Qatar and literature review","volume":"188","author":"Ali","year":"2022","journal-title":"Am J Med Genet A"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1155\/crpe\/9913412","article-title":"DCAF17 mutation in woodhouse\u2013sakati syndrome: A case report on a novel homozygous variant","volume":"2025","author":"Khalili Dehkordi","year":"2025","journal-title":"Case Rep Pediatr"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1210\/jcemcr\/luae130","article-title":"Woodhouse-sakati syndrome: the new genetic variant of DCAF17 in 2 adult sisters","volume":"2","author":"Amosova","year":"2024","journal-title":"JCEM Case Rep"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.32225","article-title":"Three siblings with woodhouse-sakati syndrome: A case report of A new Saudi family","volume":"14","author":"Alhuzaim","year":"2022","journal-title":"Cureus"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.770871","article-title":"Case report: A Chinese family of woodhouse-sakati syndrome with diabetes mellitus, with a novel biallelic deletion mutation of the DCAF17 gene","volume":"12","author":"Zhou","year":"2021","journal-title":"Front Endocrinol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s40618-013-0001-5","article-title":"Endocrine disorders in Woodhouse-Sakati syndrome: a systematic review of the literature","volume":"37","author":"Agopiantz","year":"2014","journal-title":"J Endocrinol Invest"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13183","article-title":"Novel inactivating mutations of the DCAF17 gene in American and Turkish families cause male infertility and female subfertility in the mouse model","volume":"93","author":"Gurbuz","year":"2018","journal-title":"Clin Genet"},{"key":"B40","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s13023-023-02614-8","article-title":"Genetic epidemiology of Woodhouse-Sakati Syndrome in the Greater Middle East region and beyond: a systematic review","volume":"18","author":"Kohil","year":"2023","journal-title":"Orphanet J Rare Dis"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.829153","article-title":"Ovarian reserve and ART\u00a0outcomes in blepharophimosis-ptosis-epicanthus inversus syndrome patients with FOXL2 mutations","volume":"13","author":"Meng","year":"2022","journal-title":"Front Endocrinol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(03)14069-x","article-title":"LMNA mutations in atypical Werner\u2019s syndrome","volume":"362","author":"Chen","year":"2003","journal-title":"Lancet"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32627","article-title":"Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation","author":"McPherson","year":"2009","journal-title":"Am J Med Genet A"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/ehjcr\/ytaf110","article-title":"A case report of non-lamin A\/C dilated cardiomyopathy presenting in a patient with Najjar\u2013Malouf syndrome","volume":"9","author":"Flury","year":"2025","journal-title":"Eur Heart J - Case Rep"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2013.1669","article-title":"Dilated cardiomyopathy and ovarian dysgenesis in a patient with Malouf syndrome: A case report","volume":"8","author":"Gersak","year":"2013","journal-title":"Mol Med Rep"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.15829\/1560-4071-2016-11-90-94","article-title":"An orphan phenotype of cardiogenital laminopathy \u2014 Malouf syndrome","author":"Vaykhanskaya","year":"2016","journal-title":"Russ J Cardiol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00975","article-title":"Disruption of spermatogenesis in mice lacking A-type lamins","volume":"117","author":"Alsheimer","year":"2004","journal-title":"J Cell Sci"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1172\/JCI162315","article-title":"TP63 gain-of-function mutations cause premature ovarian insufficiency by inducing oocyte apoptosis","volume":"133","author":"Huang","year":"2023","journal-title":"J Clin Invest"},{"key":"B49","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1186\/s12958-024-01309-4","article-title":"Identification of novel variants and candidate genes in women with 46,XX complete gonadal dysgenesis","volume":"22","author":"Ding","year":"2024","journal-title":"Reprod Biol Endocrinol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23744","article-title":"TP63-truncating variants cause isolated premature ovarian insufficiency","volume":"40","author":"Tucker","year":"2019","journal-title":"Hum Mutat"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-023-02886-w","article-title":"Heterozygous TP63 pathogenic variants in isolated primary ovarian\u00a0insufficiency","volume":"40","author":"Vanderschelden","year":"2023","journal-title":"J Assist Reprod Genet"},{"key":"B52","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1146\/annurev-genom-110122-090239","article-title":"Meiotic chromosome structure, the synaptonemal complex, and infertility","volume":"24","author":"Adams","year":"2023","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1002\/embj.201387330","article-title":"Meiotic cohesin STAG3 is required for\u00a0chromosome axis formation and sister chromatid cohesion","volume":"33","author":"Winters","year":"2014","journal-title":"EMBO J"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-025-03417-5","article-title":"Novel STAG3 variant causes oligoasthenoteratozoospermia with high sperm aneuploidy rate","volume":"42","author":"Tsabai","year":"2025","journal-title":"J Assist Reprod Genet"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.142","article-title":"Comprehensive use of extended exome analysis improves diagnostic yield in rare disease: a retrospective survey in 1,059 cases","volume":"20","author":"Bergant","year":"2018","journal-title":"Genet Med"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaaa050","article-title":"STAG3 homozygous missense variant causes primary ovarian insufficiency and male non-obstructive azoospermia","volume":"26","author":"Jaillard","year":"2020","journal-title":"Mol Hum Reprod"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2022.146281","article-title":"Novel STAG3 variant associated with primary ovarian insufficiency and non-obstructive azoospermia in an Iranian consanguineous family","volume":"821","author":"Akbari","year":"2022","journal-title":"Gene"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1007\/s00438-019-01594-4","article-title":"Novel STAG3 mutations in a Caucasian family with primary ovarian insufficiency","volume":"294","author":"Heddar","year":"2019","journal-title":"Mol Genet Genomics"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0916-0","article-title":"A genomics approach to male infertility","volume":"22","author":"Alhathal","year":"2020","journal-title":"Genet Med"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad154","article-title":"SPIDR is required for homologous recombination during mammalian meiosis","volume":"51","author":"Huang","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2714","article-title":"A biallelic mutation in the homologous recombination repair gene SPIDR is associated with human gonadal dysgenesis","volume":"102","author":"Smirin-Yosef","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14080","article-title":"SPIDR\n             homozygous nonsense pathogenic variant in isolated primary ovarian insufficiency with chromosomal instability","volume":"101","author":"Heddar","year":"2022","journal-title":"Clin Genet"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-1291","article-title":"Deletion of CPEB1 gene: A rare but recurrent cause of premature ovarian insufficiency","volume":"101","author":"Hyon","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dey389","article-title":"High-resolution array-CGH analysis on 46,XX patients affected by early onset primary ovarian insufficiency discloses new genes involved in ovarian function","volume":"34","author":"Bestetti","year":"2019","journal-title":"Hum Reprod"},{"key":"B65","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s12920-020-00787-w","article-title":"A 15q25.2 microdeletion phenotype for premature ovarian failure in a Chinese girl: a case report and review of literature","volume":"13","author":"Chen","year":"2020","journal-title":"BMC Med Genomics"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy261","article-title":"Basonuclin 1 deficiency is a cause of primary ovarian insufficiency","volume":"27","author":"Zhang","year":"2018","journal-title":"Hum Mol Genet"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33323-8","article-title":"BNC1 deficiency-triggered ferroptosis through the NF2-YAP pathway induces primary ovarian insufficiency","volume":"13","author":"Wang","year":"2022","journal-title":"Nat Commun"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-35994-3","article-title":"CPEB1-dependent disruption of the mRNA translation program in oocytes during maternal aging","volume":"14","author":"Takahashi","year":"2023","journal-title":"Nat Commun"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.075903","article-title":"Recurrent microdeletions of 15q25.2 are associated with increased risk of congenital diaphragmatic hernia, cognitive deficits and possibly Diamond-Blackfan anaemia","volume":"47","author":"Wat","year":"2010","journal-title":"J Med Genet"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1013894","article-title":"Identification and characterization of novel compound heterozygous variants in FSHR causing primary ovarian insufficiency with resistant ovary syndrome","volume":"13","author":"Chen","year":"2023","journal-title":"Front Endocrinol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63924","article-title":"Identification and characterization of novel FSHR copy number variations causing premature ovarian insufficiency","volume":"197","author":"Lokchine","year":"2025","journal-title":"Am J Med Genet A"},{"key":"B72","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.rbmo.2018.11.011","article-title":"Novel inactivating mutations in the FSH receptor cause premature ovarian insufficiency with resistant ovary syndrome","volume":"38","author":"He","year":"2019","journal-title":"Reprod BioMed Online"},{"key":"B73","doi-asserted-by":"publisher","first-page":"S1083318825002748","DOI":"10.1016\/j.jpag.2025.06.002","article-title":"FSH receptor variant: an unusual cause of secondary amenorrhea","author":"Cooper","year":"2025","journal-title":"J Pediatr Adolesc Gynecol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1530\/jme-20-0218","article-title":"Discovery of a possible role of asprosin in ovarian follicular function","volume":"66","author":"Maylem","year":"2021","journal-title":"J Mol Endocrinol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-023-02981-y","article-title":"NOBOX gene variants in premature ovarian insufficiency: ethnicity-dependent insights","volume":"41","author":"Jordan","year":"2024","journal-title":"J Assist Reprod Genet"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deaf058","article-title":"Reclassifying NOBOX variants in primary ovarian insufficiency cases with a corrected gene model and a novel quantitative framework","volume":"40","author":"Veitia","year":"2025","journal-title":"Hum Reprod"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz066","article-title":"MYRF haploinsufficiency causes 46,XY and 46,XX disorders of sex development: bioinformatics consideration","volume":"28","author":"Hamanaka","year":"2019","journal-title":"Hum Mol Genet"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11164858","article-title":"MYRF: A new regulator of cardiac and early gonadal development\u2014Insights from\u00a0single cell RNA sequencing analysis","volume":"11","author":"Calonga-Sol\u00eds","year":"2022","journal-title":"J Clin Med"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.2139","article-title":"Two sisters with cardiac-urogenital syndrome secondary to pathogenic splicing variant in the MYRF gene with unaffected parents: A case of gonadal mosaicism","volume":"11","author":"Slaba","year":"2023","journal-title":"Mol Genet Genomic Med"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007822","article-title":"De novo variants in congenital diaphragmatic hernia identify MYRF as a new syndrome and reveal genetic overlaps with other developmental disorders","volume":"14","author":"Qi","year":"2018","journal-title":"PloS Genet"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1080\/09513590.2025.2546985","article-title":"Identification of a novel variant in MYRF gene in a patient with 46, XX disorders of sex development","volume":"41","author":"Ding","year":"2025","journal-title":"Gynecol Endocrinol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.18565\/aig.2024.321","article-title":"Uterus didelphys, longitudinal vaginal septum and diminished ovarian reserve in a patient with MYRF-associated disease","author":"Tsabai","year":"2025","journal-title":"Akush Ginekol (Sofiia)"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnac013","article-title":"Hippo signaling in the ovary: emerging roles in development, fertility, and disease","volume":"43","author":"Clark","year":"2022","journal-title":"Endocr Rev"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.114.118604","article-title":"Lats1 deletion causes increased germ cell apoptosis and follicular cysts in mouse ovaries1","volume":"93","author":"Sun","year":"2015","journal-title":"Biol Reprod"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1038\/5965","article-title":"Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction","volume":"21","author":"St John","year":"1999","journal-title":"Nat Genet"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900609r","article-title":"Lats1andLats2are required for ovarian granulosa cell fate maintenance","volume":"33","author":"Tsoi","year":"2019","journal-title":"FASEB J"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.05.017","article-title":"TP53, MSH4, and LATS1 germline mutations in a family with clustering of nervous system tumors","volume":"184","author":"Kim","year":"2014","journal-title":"Am J Pathol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1687148\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T05:13:10Z","timestamp":1764220390000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1687148\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,27]]},"references-count":87,"alternative-id":["10.3389\/fendo.2025.1687148"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1687148","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,27]]},"article-number":"1687148"}}