{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:54:44Z","timestamp":1783338884995,"version":"3.54.6"},"reference-count":102,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T00:00:00Z","timestamp":1630713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health grants \u2018Ricerca Corrente\u2019","award":["08C621_2016"],"award-info":[{"award-number":["08C621_2016"]}]},{"name":"Italian Ministry of Health grants \u2018Ricerca Corrente\u2019","award":["08C924_2019"],"award-info":[{"award-number":["08C924_2019"]}]},{"name":"IRCCS Istituto Auxologico Italiano"},{"name":"\u2018Piano Sostegno alla Ricerca\u2019","award":["PSR2020_FINELLI_LINEA_B"],"award-info":[{"award-number":["PSR2020_FINELLI_LINEA_B"]}]},{"DOI":"10.13039\/100012352","name":"University of Milan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012352","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Telethon-Italy","award":["GG14181"],"award-info":[{"award-number":["GG14181"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,18]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>STUDY QUESTION<\/jats:title><jats:p>Can a targeted whole exome sequencing (WES) on a cohort of women showing a primary ovarian insufficiency (POI) phenotype at a young age, combined with a study of copy number variations, identify variants in candidate genes confirming their deleterious effect on ovarian function?<\/jats:p><\/jats:sec><jats:sec><jats:title>SUMMARY ANSWER<\/jats:title><jats:p>This integrated approach has proved effective in identifying novel candidate genes unveiling mechanisms involved in POI pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>WHAT IS KNOWN ALREADY<\/jats:title><jats:p>POI, a condition occurring in 1% of women under 40 years of age, affects women\u2019s fertility leading to a premature loss of ovarian reserve. The genetic causes of POI are highly heterogeneous and several determinants contributing to its prominent oligogenic inheritance pattern still need to be elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title><jats:p>WES screening for pathogenic variants of 41 Italian women with non-syndromic primary and early secondary amenorrhoea occurring before age 25 was replicated on another 60 POI patients, including 35 French and 25 American women, to reveal statistically significant shared variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title><jats:p>The Italian POI patients\u2019 DNA were processed by targeted WES including 542 RefSeq genes expressed or functioning during distinct reproductive or ovarian processes (e.g. DNA repair, meiosis, oocyte maturation, folliculogenesis and menopause). Extremely rare variants were filtered and selected by means of a Fisher Exact test using several publicly available datasets. A case-control Burden test was applied to highlight the most significant genes using two ad-hoc control female cohorts. To support the obtained data, the identified genes were screened on a novel cohort of 60 Caucasian POI patients and the same case-control analysis was carried out. Comparative analysis of the human identified genes was performed on mouse and Drosophila melanogaster by analysing the orthologous genes in their ovarian phenotype, and two of the selected genes were fruit fly modelled to explore their role in fertility.<\/jats:p><\/jats:sec><jats:sec><jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title><jats:p>The filtering steps applied to search for extremely rare pathogenic variants in the Italian cohort revealed 64 validated single-nucleotide variants\/Indels in 59 genes in 30 out of 41 screened women. Burden test analysis highlighted 13 ovarian genes as being the most enriched and significant. To validate these findings, filtering steps and Burden analysis on the second cohort of Caucasian patients yielded 11 significantly enriched genes. Among them, AFP, DMRT3, MOV10, FYN and MYC were significant in both patient cohorts and hence were considered strong candidates for POI. Mouse and Drosophila comparative analysis evaluated a conserved role through the evolution of several candidates, and functional studies using a Drosophila model, when applicable, supported the conserved role of the MOV10 armitage and DMRT3 dmrt93B orthologues in female fertility.<\/jats:p><\/jats:sec><jats:sec><jats:title>LARGE SCALE DATA<\/jats:title><jats:p>The datasets for the Italian cohort generated during the current study are publicly available at ClinVar database (http:\/\/www.ncbi.nlm.nih.gov\/clinvar\/): accession numbers SCV001364312 to SCV001364375.<\/jats:p><\/jats:sec><jats:sec><jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title><jats:p>This is a targeted WES analysis hunting variants in candidate genes previously identified by different genomic approaches. For most of the investigated sporadic cases, we could not track the parental inheritance, due to unavailability of the parents\u2019 DNA samples; in addition, we might have overlooked additional rare variants in novel candidate POI genes extracted from the exome data. On the contrary, we might have considered some inherited variants whose clinical significance is uncertain and might not be causative for the patients\u2019 phenotype. Additionally, as regards the Drosophila model, it will be extremely important in the future to have more mutants or RNAi strains available for each candidate gene in order to validate their role in POI pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title><jats:p>The genomic, statistical, comparative and functional approaches integrated in our study convincingly support the extremely heterogeneous oligogenic nature of POI, and confirm the maintenance across the evolution of some key genes safeguarding fertility and successful reproduction. Two principal classes of genes were identified: (i) genes primarily involved in meiosis, namely in synaptonemal complex formation, asymmetric division and oocyte maturation and (ii) genes safeguarding cell maintenance (piRNA and DNA repair pathways).<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title><jats:p>This work was supported by Italian Ministry of Health grants \u2018Ricerca Corrente\u2019 (08C621_2016 and 08C924_2019) provided to IRCCS Istituto Auxologico Italiano, and by \u2018Piano Sostegno alla Ricerca\u2019 (PSR2020_FINELLI_LINEA_B) provided by the University of Milan; M.P.B. was supported by Telethon-Italy (grant number GG14181). There are no conflicts of interest.<\/jats:p><\/jats:sec>","DOI":"10.1093\/humrep\/deab192","type":"journal-article","created":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T09:41:44Z","timestamp":1630748504000},"page":"2975-2991","source":"Crossref","is-referenced-by-count":25,"title":["Targeted whole exome sequencing and Drosophila modelling to unveil the molecular basis of primary ovarian insufficiency"],"prefix":"10.1093","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8972-6737","authenticated-orcid":false,"given":"I","family":"Bestetti","sequence":"first","affiliation":[{"name":"Research Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy"},{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, Segrate, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1005-9319","authenticated-orcid":false,"given":"C","family":"Barbieri","sequence":"additional","affiliation":[{"name":"Division of Genetics and Cell Biology, San Raffaele Research Institute and Vita Salute University, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Sironi","sequence":"additional","affiliation":[{"name":"Research Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy"},{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, Segrate, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Specchia","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4809-8601","authenticated-orcid":false,"given":"S A","family":"Yatsenko","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA"},{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, Pittsburgh, PA, USA"},{"name":"Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M D","family":"De Donno","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Caslini","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, Segrate, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Gentilini","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy"},{"name":"Bioinformatics and Statistical Genomics Unit, IRCCS Istituto Auxologico Italiano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Crippa","sequence":"additional","affiliation":[{"name":"Research Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy"},{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, Segrate, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Larizza","sequence":"additional","affiliation":[{"name":"Research Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Marozzi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, Segrate, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Rajkovic","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California San Francisco, San Francisco, CA, USA"},{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San, Francisco, San Francisco, CA, USA"},{"name":"Institute of Human Genetics, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Toniolo","sequence":"additional","affiliation":[{"name":"Division of Genetics and Cell Biology, San Raffaele Research Institute and Vita Salute University, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M P","family":"Bozzetti","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8464-6906","authenticated-orcid":false,"given":"P","family":"Finelli","sequence":"additional","affiliation":[{"name":"Research Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy"},{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, Segrate, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,9,4]]},"reference":[{"key":"2021111806391777800_deab192-B1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"1000 Genomes Project Consortium","year":"2015","journal-title":"Nature"},{"key":"2021111806391777800_deab192-B2","doi-asserted-by":"crossref","first-page":"4540","DOI":"10.1210\/jc.2009-0186","article-title":"Array comparative genomic hybridization profiling analysis reveals deoxyribonucleic acid copy number variations associated with premature ovarian failure","volume":"94","author":"Aboura","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"2021111806391777800_deab192-B3","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/cge.13803","article-title":"An exome-wide exploration of cases of primary ovarian insufficiency uncovers novel sequence variants and candidate genes","volume":"98","author":"Alvarez-Mora","year":"2020","journal-title":"Clin Genet"},{"key":"2021111806391777800_deab192-B4","doi-asserted-by":"crossref","first-page":"4545","DOI":"10.4161\/cc.22819","article-title":"p63 the guardian of human reproduction","volume":"11","author":"Amelio","year":"2012","journal-title":"Cell Cycle"},{"key":"2021111806391777800_deab192-B5","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.mod.2014.06.001","article-title":"A role for Drosophila Cyclin J in oogenesis revealed by genetic interactions with the piRNA pathway","volume":"133","author":"Atikukke","year":"2014","journal-title":"Mech Dev"},{"key":"2021111806391777800_deab192-B6","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1083\/jcb.200811079","article-title":"RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation","volume":"185","author":"Badie","year":"2009","journal-title":"J Cell Biol"},{"key":"2021111806391777800_deab192-B8","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.molcel.2018.06.030","article-title":"FANCA promotes DNA double-strand break repair by catalyzing single-strand annealing and strand exchange","volume":"71","author":"Benitez","year":"2018","journal-title":"Mol Cell"},{"key":"2021111806391777800_deab192-B9","doi-asserted-by":"crossref","first-page":"574","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":"2021111806391777800_deab192-B10","doi-asserted-by":"crossref","first-page":"4541","DOI":"10.1210\/jc.2016-2152","article-title":"Identification of multiple gene mutations accounts for a new genetic architecture of primary ovarian insufficiency","volume":"101","author":"Bouilly","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"2021111806391777800_deab192-B11","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1242\/jcs.161810","article-title":"The Drosophila fragile X mental retardation protein participates in the piRNA pathway","volume":"128","author":"Bozzetti","year":"2015","journal-title":"J Cell Sci"},{"key":"2021111806391777800_deab192-B12","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1093\/humrep\/dew025","article-title":"A novel follicle-stimulating hormone receptor mutation causing primary ovarian failure: a fertility application of whole exome sequencing","volume":"31","author":"Bramble","year":"2016","journal-title":"Hum Reprod"},{"key":"2021111806391777800_deab192-B13","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.neuron.2009.07.004","article-title":"Mammalian Par3 regulates progenitor cell asymmetric division via notch signaling in the developing neocortex","volume":"63","author":"Bultje","year":"2009","journal-title":"Neuron"},{"key":"2021111806391777800_deab192-B14","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1056\/NEJMoa1309635","article-title":"Mutant cohesin in premature ovarian failure","volume":"370","author":"Caburet","year":"2014","journal-title":"N Engl J Med"},{"key":"2021111806391777800_deab192-B15","first-page":"3161","article-title":"A homozygous donor splice-site mutation in the meiotic gene MSH4 causes primary ovarian insufficiency","volume":"26","author":"Carlosama","year":"2017","journal-title":"Hum Mol Genet"},{"key":"2021111806391777800_deab192-B16","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/humu.23153","article-title":"Rare deleterious PARD3 variants in the aPKC-binding region are implicated in the pathogenesis of human cranial neural tube defects via disrupting apical tight junction formation","volume":"38","author":"Chen","year":"2017","journal-title":"Hum Mutat"},{"key":"2021111806391777800_deab192-B18","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/ejhg.2012.113","article-title":"Small effective population size and genetic homogeneity in the Val Borbera isolate","volume":"21","author":"Colonna","year":"2013","journal-title":"Eur J Hum Genet"},{"key":"2021111806391777800_deab192-B19","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S0092-8674(04)00250-8","article-title":"The Drosophila SDE3 homolog armitage is required for oskar mRNA silencing and embryonic axis speci\ufb01cation","volume":"116","author":"Cook","year":"2004","journal-title":"Cell"},{"key":"2021111806391777800_deab192-B20","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3389\/fphys.2019.00133","article-title":"The RNA helicase BELLE is involved in circadian rhythmicity and in transposons regulation in Drosophila melanogaster","volume":"10","author":"Cusumano","year":"2019","journal-title":"Front Physiol"},{"key":"2021111806391777800_deab192-B21","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1101\/gad.7.4.671","article-title":"A null c-myc mutation causes lethality before 10.5 days of gestation in homozygotes and reduced fertility in heterozygous female mice","volume":"7","author":"Davis","year":"1993","journal-title":"Genes Dev"},{"key":"2021111806391777800_deab192-B22","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/ng.3841","article-title":"Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk","volume":"49","author":"Day","year":"2017","journal-title":"Nat Genet"},{"key":"2021111806391777800_deab192-B23","first-page":"82","article-title":"Alpha-fetoprotein: from a diagnostic biomarker to a key role in female fertility","volume":"1","author":"De Mees","year":"2007","journal-title":"Biomark Insights"},{"key":"2021111806391777800_deab192-B24","doi-asserted-by":"crossref","first-page":"E2129","DOI":"10.1210\/jc.2014-1268","article-title":"Exome sequencing reveals SYCE1 mutation associated with autosomal recessive primary ovarian insufficiency","volume":"99","author":"de Vries","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"2021111806391777800_deab192-B25","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":"2021111806391777800_deab192-B26","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/1477-7827-6-60","article-title":"Granulosa cells express three inositol 1,4,5-trisphosphate receptor isoforms: cytoplasmic and nuclear Ca2+ mobilization","volume":"6","author":"D\u00edaz-Mu\u00f1oz","year":"2008","journal-title":"Reprod Biol Endocrinol"},{"key":"2021111806391777800_deab192-B27","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ydbio.2005.05.012","article-title":"Src64 is involved in fusome development and karyosome formation during Drosophila oogenesis","volume":"284","author":"Djagaeva","year":"2005","journal-title":"Dev Biol"},{"key":"2021111806391777800_deab192-B28","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1093\/humrep\/deq284","article-title":"Array comparative genomic hybridization for the detection of submicroscopic copy number variations of the X chromosome in women with premature ovarian failure","volume":"25","author":"Dudding","year":"2010","journal-title":"Hum Reprod"},{"key":"2021111806391777800_deab192-B29","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ydbio.2004.12.034","article-title":"PAR-3 defines a central subdomain of the cortical actin cap in mouse eggs","volume":"280","author":"Duncan","year":"2005","journal-title":"Dev Biol"},{"key":"2021111806391777800_deab192-B30","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1534\/genetics.119.302558","article-title":"Germ cell lineage homeostasis in Drosophila requires the Vasa RNA helicase","volume":"213","author":"Durdevic","year":"2019","journal-title":"Genetics"},{"key":"2021111806391777800_deab192-B31","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/cge.12736","article-title":"A non-sense MCM9 mutation in a familial case of primary ovarian insufficiency","volume":"89","author":"Fauchereau","year":"2016","journal-title":"Clin Genet"},{"key":"2021111806391777800_deab192-B32","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.fertnstert.2015.04.016","article-title":"Next generation sequencing in women affected by nonsyndromic premature ovarian failure displays new potential causative genes and mutations","volume":"104","author":"Fonseca","year":"2015","journal-title":"Fertil Steril"},{"key":"2021111806391777800_deab192-B33","doi-asserted-by":"crossref","first-page":"bvz037","DOI":"10.1210\/jendso\/bvz037","article-title":"Genetics of primary ovarian insufficiency in the next-generation sequencing era","volume":"4","author":"Fran\u00e7a","year":"2019","journal-title":"J Endocr Soc"},{"key":"2021111806391777800_deab192-B34","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12915-019-0659-z","article-title":"Biological and RNA regulatory function of MOV10 in mammalian germ cells","volume":"17","author":"Fu","year":"2019","journal-title":"BMC Biol"},{"key":"2021111806391777800_deab192-B35","doi-asserted-by":"crossref","first-page":"12865","DOI":"10.1073\/pnas.202215399","article-title":"Alpha-fetoprotein, the major fetal serum protein, is not essential for embryonic development but is required for female fertility","volume":"99","author":"Gabant","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021111806391777800_deab192-B36","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1093\/bib\/bbr042","article-title":"Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium","volume":"12","author":"Gaudet","year":"2011","journal-title":"Brief Bioinform"},{"key":"2021111806391777800_deab192-B37","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/j.molcel.2019.04.006","article-title":"The RNA-binding ATPase, armitage, couples piRNA amplification in nuage to phased piRNA production on mitochondria","volume":"74","author":"Ge","year":"2019","journal-title":"Mol Cell"},{"key":"2021111806391777800_deab192-B38","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.18632\/aging.101885","article-title":"SIRT6 participates in the quality control of aged oocytes via modulating telomere function","volume":"11","author":"Ge","year":"2019","journal-title":"Aging (Albany, NY)"},{"key":"2021111806391777800_deab192-B39","doi-asserted-by":"crossref","first-page":"5714","DOI":"10.3390\/molecules25235714","article-title":"DNA damaged induced cell death in oocytes","volume":"25","author":"Gebel","year":"2020","journal-title":"Molecules"},{"key":"2021111806391777800_deab192-B40","doi-asserted-by":"crossref","first-page":"4836","DOI":"10.1038\/onc.2016.16","article-title":"Rad54 and Mus81 cooperation promotes DNA damage repair and restrains chromosome missegregation","volume":"35","author":"Ghamrasni","year":"2016","journal-title":"Oncogene"},{"key":"2021111806391777800_deab192-B41","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1038\/s41598-017-02071-x","article-title":"Regulation of GVBD in mouse oocytes by miR-125a-3p and Fyn kinase through modulation of actin filaments","volume":"7","author":"Grossman","year":"2017","journal-title":"Sci Rep"},{"key":"2021111806391777800_deab192-B42","doi-asserted-by":"crossref","first-page":"15366","DOI":"10.1038\/srep15366","article-title":"Sirt6 depletion causes spindle defects and chromosome misalignment during meiosis of mouse oocyte","volume":"5","author":"Han","year":"2015","journal-title":"Sci Rep"},{"key":"2021111806391777800_deab192-B43","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.gde.2011.08.011","article-title":"Shining light on Drosophila oogenesis: live imaging of egg development","volume":"21","author":"He","year":"2011","journal-title":"Curr Opin Genet Dev"},{"key":"2021111806391777800_deab192-B44","doi-asserted-by":"crossref","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":"2021111806391777800_deab192-B45","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s00418-012-1051-z","article-title":"WHAMM is required for meiotic spindle migration and asymmetric cytokinesis in mouse oocytes","volume":"139","author":"Huang","year":"2013","journal-title":"Histochem Cell Biol"},{"key":"2021111806391777800_deab192-B46","doi-asserted-by":"crossref","first-page":"2099","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":"2021111806391777800_deab192-B47","doi-asserted-by":"crossref","first-page":"783","DOI":"10.15252\/embr.201642544","article-title":"The cohesin REC8 prevents illegitimate inter-sister synaptonemal complex assembly","volume":"17","author":"Ishiguro","year":"2016","journal-title":"EMBO Rep"},{"key":"2021111806391777800_deab192-B48","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1016\/j.celrep.2019.04.029","article-title":"Distinct and collaborative functions of Yb and armitage in transposon-targeting piRNA biogenesis","volume":"27","author":"Ishizu","year":"2019","journal-title":"Cell Rep"},{"key":"2021111806391777800_deab192-B49","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s13048-016-0272-5","article-title":"Array-CGH diagnosis in ovarian failure: identification of new molecular actors for ovarian physiology","volume":"9","author":"Jaillard","year":"2016","journal-title":"J Ovarian Res"},{"key":"2021111806391777800_deab192-B50","doi-asserted-by":"crossref","first-page":"3049","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":"2021111806391777800_deab192-B51","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.blre.2018.03.007","article-title":"The roles of JAK2 in DNA damage and repair in the myeloproliferative neoplasms: opportunities for targeted therapy","volume":"32","author":"Karantanos","year":"2018","journal-title":"Blood Rev"},{"key":"2021111806391777800_deab192-B52","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"2021111806391777800_deab192-B53","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1242\/dev.01025","article-title":"Gbb\/Bmp signaling is essential for maintaining germline stem cells and for repressing bam transcription in the Drosophila testis","volume":"131","author":"Kawase","year":"2004","journal-title":"Development"},{"key":"2021111806391777800_deab192-B54","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.fertnstert.2010.07.1067","article-title":"Epistasis between CYP19A1 and ESR1 polymorphisms is associated with premature ovarian failure","volume":"95","author":"Kim","year":"2011","journal-title":"Fertil Steril"},{"key":"2021111806391777800_deab192-B56","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/j.cell.2009.07.014","article-title":"The Drosophila HP1 homolog Rhino is required for transposon silencing and piRNA production by dual-strand clusters","volume":"138","author":"Klattenhoff","year":"2009","journal-title":"Cell"},{"key":"2021111806391777800_deab192-B57","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1016\/j.fertnstert.2011.01.018","article-title":"Copy number variants on the X chromosome in women with primary ovarian insufficiency","volume":"95","author":"Knauff","year":"2011","journal-title":"Fertil Steril"},{"key":"2021111806391777800_deab192-B58","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: the human genomic variant search engine","volume":"35","author":"Kopanos","year":"2019","journal-title":"Bioinformatics"},{"key":"2021111806391777800_deab192-B59","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.mce.2015.05.005","article-title":"Aetiological coding sequence variants in non-syndromic premature ovarian failure: from genetic linkage analysis to next generation sequencing","volume":"411","author":"Laissue","year":"2015","journal-title":"Mol Cell Endocrinol"},{"key":"2021111806391777800_deab192-B60","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1159\/000314958","article-title":"Copy number variants in premature ovarian failure and ovarian dysgenesis","volume":"4","author":"Ledig","year":"2010","journal-title":"Sex Dev"},{"key":"2021111806391777800_deab192-B61","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"key":"2021111806391777800_deab192-B62","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.4161\/cc.9.8.11299","article-title":"The involvement of Fyn kinase in resumption of the first meiotic division in mouse oocytes","volume":"9","author":"Levi","year":"2010","journal-title":"Cell Cycle"},{"key":"2021111806391777800_deab192-B63","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1530\/REP-10-0312","article-title":"Fyn kinase is involved in cleavage furrow ingression during meiosis and mitosis","volume":"140","author":"Levi","year":"2010","journal-title":"Reproduction"},{"key":"2021111806391777800_deab192-B64","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler Transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2021111806391777800_deab192-B65","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.ajhg.2017.01.004","article-title":"InterVar: clinical interpretation of genetic variants by ACMG-AMP 2015 guideline","volume":"100","author":"Li","year":"2017","journal-title":"Am J Hum Genet"},{"key":"2021111806391777800_deab192-B66","doi-asserted-by":"crossref","first-page":"6714","DOI":"10.1073\/pnas.0701920104","article-title":"Unique germ-line organelle, nuage, functions to repress selfish genetic elements in Drosophila melanogaster","volume":"104","author":"Lim","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021111806391777800_deab192-B67","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1534\/g3.117.042390","article-title":"The genetic architecture of ovariole number in Drosophila melanogaster: genes with major, quantitative, and pleiotropic effects","volume":"7","author":"Lobell","year":"2017","journal-title":"G3 (Bethesda)"},{"key":"2021111806391777800_deab192-B68","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1071\/RD09311","article-title":"Role of Fyn kinase in oocyte developmental potential","volume":"22","author":"Luo","year":"2010","journal-title":"Reprod Fertil Dev"},{"key":"2021111806391777800_deab192-B69","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1242\/dev.00932","article-title":"Drosophila dMyc is required for ovary cell growth and endoreplication","volume":"131","author":"Maines","year":"2004","journal-title":"Development"},{"key":"2021111806391777800_deab192-B70","doi-asserted-by":"crossref","first-page":"e2001164","DOI":"10.1371\/journal.pbio.2001164","article-title":"The mismatch repair and meiotic recombination endonuclease Mlh1-Mlh3 is activated by polymer formation and can cleave DNA substrates in trans","volume":"15","author":"Manhart","year":"2017","journal-title":"PLoS Biol"},{"key":"2021111806391777800_deab192-B71","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1111\/cge.13725","article-title":"Novel phenotype of syndromic premature ovarian insufficiency associated with TP63 molecular defect","volume":"97","author":"Mathorne","year":"2020","journal-title":"Clin Genet"},{"key":"2021111806391777800_deab192-B72","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1016\/j.fertnstert.2010.12.052","article-title":"Genomic analysis using high-resolution single-nucleotide polymorphism arrays reveals novel microdeletions associated with premature ovarian failure","volume":"95","author":"McGuire","year":"2011","journal-title":"Fertil Steril"},{"key":"2021111806391777800_deab192-B73","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","article-title":"The ensembl variant effect predictor","volume":"17","author":"McLaren","year":"2016","journal-title":"Genome Biol"},{"key":"2021111806391777800_deab192-B74","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1016\/j.cub.2006.08.051","article-title":"The role of PIWI and the miRNA machinery in Drosophila germline determination","volume":"16","author":"Megosh","year":"2006","journal-title":"Curr Biol"},{"key":"2021111806391777800_deab192-B75","doi-asserted-by":"crossref","first-page":"8722","DOI":"10.1038\/s41598-018-26928-x","article-title":"Reelin and aromatase cooperate in ovarian follicle development","volume":"8","author":"Meseke","year":"2018","journal-title":"Sci Rep"},{"key":"2021111806391777800_deab192-B76","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1210\/js.2016-1014","article-title":"POLR2C mutations are associated with primary ovarian insufficiency in women","volume":"1","author":"Moriwaki","year":"2017","journal-title":"J Endocr Soc"},{"key":"2021111806391777800_deab192-B77","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/gepi.20450","article-title":"An evaluation of statistical approaches to rare variant analysis in genetic association studies","volume":"34","author":"Morris","year":"2010","journal-title":"Genet Epidemiol"},{"key":"2021111806391777800_deab192-B78","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.molcel.2004.08.009","article-title":"The Fanconi anaemia gene FANCC promotes homologous recombination and error-prone DNA repair","volume":"15","author":"Niedzwiedz","year":"2004","journal-title":"Mol Cell"},{"key":"2021111806391777800_deab192-B79","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1093\/humrep\/deu149","article-title":"Identification of a duplication within the GDF9 gene and novel candidate genes for primary ovarian insufficiency (POI) by a customized high-resolution array comparative genomic hybridization platform","volume":"29","author":"Norling","year":"2014","journal-title":"Hum Reprod"},{"key":"2021111806391777800_deab192-B80","doi-asserted-by":"crossref","first-page":"3301","DOI":"10.1038\/emboj.2010.212","article-title":"An in vivo RNAi assay identifies major genetic and cellular requirements for primary piRNA biogenesis in Drosophila","volume":"29","author":"Olivieri","year":"2010","journal-title":"EMBO J"},{"key":"2021111806391777800_deab192-B81","doi-asserted-by":"crossref","first-page":"e51636","DOI":"10.7554\/eLife.51636","article-title":"SIRT6 is a DNA double-strand break sensor","volume":"9","author":"Onn","year":"2020","journal-title":"Elife"},{"key":"2021111806391777800_deab192-B82","doi-asserted-by":"crossref","first-page":"3515","DOI":"10.1242\/jcs.073890","article-title":"Drosophila I-R hybrid dysgenesis is associated with catastrophic meiosis and abnormal zygote formation","volume":"123","author":"Orsi","year":"2010","journal-title":"J Cell Sci"},{"key":"2021111806391777800_deab192-B83","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1093\/humrep\/dex089","article-title":"New mutations in non-syndromic primary ovarian insufficiency patients identified via whole-exome sequencing","volume":"32","author":"Pati\u00f1o","year":"2017","journal-title":"Hum Reprod"},{"key":"2021111806391777800_deab192-B84","doi-asserted-by":"crossref","first-page":"e1005419","DOI":"10.1371\/journal.pgen.1005419","article-title":"CSB-PGBD3 mutations cause premature ovarian failure","volume":"11","author":"Qin","year":"2015","journal-title":"PLoS Genet"},{"key":"2021111806391777800_deab192-B85","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1093\/humrep\/deq158","article-title":"Analysis of X chromosome genomic DNA sequence copy number variation associated with premature ovarian failure (POF)","volume":"25","author":"Quilter","year":"2010","journal-title":"Hum Reprod"},{"key":"2021111806391777800_deab192-B86","doi-asserted-by":"crossref","first-page":"405","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":"2021111806391777800_deab192-B87","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1101\/gad.1989510","article-title":"Roles for the Yb body components Armitage and Yb in primary piRNA biogenesis in Drosophila","volume":"24","author":"Saito","year":"2010","journal-title":"Genes Dev"},{"key":"2021111806391777800_deab192-B89","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1101\/gr.9.8.677","article-title":"dbSNP-database for single nucleotide polymorphisms and other classes of minor genetic variation","volume":"9","author":"Sherry","year":"1999","journal-title":"Genome Res"},{"key":"2021111806391777800_deab192-B90","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.3390\/ijms18051066","article-title":"dFmr1 plays roles in small RNA pathways of Drosophila melanogaster","volume":"18","author":"Specchia","year":"2017","journal-title":"Int J Mol Sci"},{"key":"2021111806391777800_deab192-B91","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3389\/fgene.2019.00010","article-title":"Drosophila melanogaster as a model to study the multiple phenotypes, related to genome stability of the fragile-X syndrome","volume":"10","author":"Specchia","year":"2019","journal-title":"Front Genet"},{"key":"2021111806391777800_deab192-B92","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/ng.1051","article-title":"Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways","volume":"44","author":"Stolk","year":"2012","journal-title":"Nat Genet"},{"key":"2021111806391777800_deab192-B93","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S1534-5807(01)00025-9","article-title":"Germ cell differentiation and synaptonemal complex formation are disrupted in CPEB knockout mice","volume":"1","author":"Tay","year":"2001","journal-title":"Dev Cell"},{"key":"2021111806391777800_deab192-B94","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/S0092-8674(04)00218-1","article-title":"RISC assembly defects in the Drosophila RNAi mutant armitage","volume":"116","author":"Tomari","year":"2004","journal-title":"Cell"},{"key":"2021111806391777800_deab192-B95","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1017\/S0967199412000287","article-title":"Participation of IP3R, RyR and L-type Ca2+ channel in the nuclear maturation of Rhinella arenarum oocytes","volume":"22","author":"Toranzo","year":"2014","journal-title":"Zygote"},{"key":"2021111806391777800_deab192-B96","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1093\/humrep\/dew142","article-title":"Copy number variation analysis detects novel candidate genes involved in follicular growth and oocyte maturation in a cohort of premature ovarian failure cases","volume":"31","author":"T\u0161uiko","year":"2016","journal-title":"Hum Reprod"},{"key":"2021111806391777800_deab192-B97","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1038\/s41431-018-0140-4","article-title":"Identification of variants in pleiotropic genes causing \u201cisolated\u201d premature ovarian insufficiency: implications for medical practice","volume":"26","author":"Tucker","year":"2018","journal-title":"Eur J Hum Genet"},{"key":"2021111806391777800_deab192-B98","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41594-018-0035-7","article-title":"Oocyte DNA damage quality control requires consecutive interplay of CHK2 and CK1 to activate p63","volume":"25","author":"Tuppi","year":"2018","journal-title":"Nat Struct Mol Biol"},{"key":"2021111806391777800_deab192-B99","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41594-018-0041-9","article-title":"TAp63 as a guardian of female germ line integrity","volume":"25","author":"Xian","year":"2018","journal-title":"Nat Struct Mol Biol"},{"key":"2021111806391777800_deab192-B100","doi-asserted-by":"crossref","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":"2021111806391777800_deab192-B101","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1093\/jmcb\/mju045","article-title":"CHK2 kinase in the DNA damage response and beyond","volume":"6","author":"Zannini","year":"2014","journal-title":"J Mol Cell Biol"},{"key":"2021111806391777800_deab192-B102","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1093\/bioinformatics\/btw079","article-title":"RVTESTS: an efficient and comprehensive tool for rare variant association analysis using sequence data","volume":"32","author":"Zhan","year":"2016","journal-title":"Bioinformatics"},{"key":"2021111806391777800_deab192-B103","doi-asserted-by":"crossref","first-page":"3787","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":"2021111806391777800_deab192-B104","doi-asserted-by":"crossref","first-page":"2926","DOI":"10.1210\/en.2018-00189","article-title":"BMP6 downregulates GDNF expression through SMAD1\/5 and ERK1\/2 signaling pathways in human granulosa-lutein cells","volume":"159","author":"Zhang","year":"2018","journal-title":"Endocrinology"},{"key":"2021111806391777800_deab192-B105","first-page":"841","article-title":"Genome-wide copy number scan in Chinese patients with premature ovarian failure]","volume":"45","author":"Zhen","year":"2013","journal-title":"Beijing Da Xue Xue Bao Yi Xue Ban"},{"key":"2021111806391777800_deab192-B106","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s13048-019-0598-x","article-title":"Persistently elevated alpha-fetoprotein associated with chronic hepatitis B during chemotherapy for malignant ovarian germ cell tumors: a case series and a review of the literature","volume":"12","author":"Zong","year":"2019","journal-title":"J Ovarian Res"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/36\/11\/2975\/41165274\/deab192.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/36\/11\/2975\/41165274\/deab192.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,8]],"date-time":"2023-01-08T16:18:33Z","timestamp":1673194713000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/36\/11\/2975\/6363989"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,4]]},"references-count":102,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,9,4]]},"published-print":{"date-parts":[[2021,10,18]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/deab192","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,11,1]]},"published":{"date-parts":[[2021,9,4]]}}}