{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:15:58Z","timestamp":1785143758585,"version":"3.55.0"},"reference-count":16,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Pathogenic germline variants in the\n                    <jats:italic>FOXL2<\/jats:italic>\n                    gene are associated with Blepharophimosis, Ptosis, and Epicanthus Inversus syndrome (BPES) in humans, an autosomal dominant condition. Two forms of BPES have emerged: (i) type I (BPES\u2010I), characterized by ocular signs and primary ovarian failure (POI), and (ii) type II (BPES\u2010II) with no systemic associations. This study aimed to compare the distribution of\n                    <jats:italic>FOXL2<\/jats:italic>\n                    variants in idiopathic POI\/DOR (diminished ovarian reserve) and both types of BPES, and to determine the involvement of FOXL2 in non\u2010syndromic forms of POI\/DOR. We studied the whole coding region of the\n                    <jats:italic>FOXL2<\/jats:italic>\n                    gene using next\u2010generation sequencing in 1282 patients with non\u2010syndromic POI\/DOR. Each identified\n                    <jats:italic>FOXL2<\/jats:italic>\n                    variant was compared to its frequency in the general population, considering ethnicity. Screening of the entire coding region of the\n                    <jats:italic>FOXL2<\/jats:italic>\n                    gene allowed us to identify 10 different variants, including nine missense variants. Of the patients with POI\/DOR, 14 (1%) carried a\n                    <jats:italic>FOXL2<\/jats:italic>\n                    variant. Significantly, six out of nine missense variants (67%) were overrepresented in our POI\/DOR cohort compared to the general or specific ethnic subgroups. Our findings strongly suggest that five rare missense variants, mainly located in the C\u2010terminal region of FOXL2 are high\u2010risk factors for non\u2010syndromic POI\/DOR, though\n                    <jats:italic>FOXL2<\/jats:italic>\n                    gene implication accounts for approximately 0.54% of non\u2010syndromic POI\/DOR cases. These results support the implementation of routine genetic screening for patients with POI\/DOR in clinical settings.\n                  <\/jats:p>","DOI":"10.1111\/cge.14526","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T05:08:46Z","timestamp":1711948126000},"page":"102-108","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Shifting the landscape: Dominant C\u2010terminal rare missense\n                    <scp>\n                      <i>FOXL2<\/i>\n                    <\/scp>\n                    variants in non\u2010syndromic primary ovarian failure etiology"],"prefix":"10.1111","volume":"106","author":[{"given":"P\u00e9n\u00e9lope","family":"Jordan","sequence":"first","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique des Maladies de Syst\u00e8me et d'Organe H\u00f4pital Cochin, APHP. Centre Universit\u00e9 de Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0524-4827","authenticated-orcid":false,"given":"Camille","family":"Verebi","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique des Maladies de Syst\u00e8me et d'Organe H\u00f4pital Cochin, APHP. Centre Universit\u00e9 de Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9r\u00e9nice","family":"Herv\u00e9","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique des Maladies de Syst\u00e8me et d'Organe H\u00f4pital Cochin, APHP. Centre Universit\u00e9 de Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Perol","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Gyn\u00e9cologie M\u00e9dicale APHP. Centre Universit\u00e9 Paris Cit\u00e9, H\u00f4pital Cochin  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeina","family":"Chakhtoura","sequence":"additional","affiliation":[{"name":"D\u00e9partement d'Endocrinologie et M\u00e9decine de la Reproduction APHP. Sorbonne Universit\u00e9, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Center for Rare Endocrine and Gynecological Disorders, ERN\u2010HCP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Courtillot","sequence":"additional","affiliation":[{"name":"D\u00e9partement d'Endocrinologie et M\u00e9decine de la Reproduction APHP. Sorbonne Universit\u00e9, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Center for Rare Endocrine and Gynecological Disorders, ERN\u2010HCP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Bachelot","sequence":"additional","affiliation":[{"name":"D\u00e9partement d'Endocrinologie et M\u00e9decine de la Reproduction APHP. Sorbonne Universit\u00e9, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Center for Rare Endocrine and Gynecological Disorders, ERN\u2010HCP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphn\u00e9","family":"Karila","sequence":"additional","affiliation":[{"name":"Service d'endocrinologie, diab\u00e9tologie et M\u00e9decine de la Reproduction APHP. Sorbonne Universit\u00e9, H\u00f4pital Saint\u2010Antoine  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Renard","sequence":"additional","affiliation":[{"name":"Service d'Endocrinologie CHU Caen  Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3846-296X","authenticated-orcid":false,"given":"Virginie","family":"Grouthier","sequence":"additional","affiliation":[{"name":"Service de Gyn\u00e9cologie M\u00e9dicale CHU de Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislas Mulot","family":"de la Croix","sequence":"additional","affiliation":[{"name":"Service d'Endocrinologie CHU Caen  Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Bernard","sequence":"additional","affiliation":[{"name":"Service de Chirurgie Gyn\u00e9cologique et M\u00e9decine de la Reproduction, Gyn\u00e9cologie M\u00e9dicale CHU Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Fouveaut","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique des Maladies de Syst\u00e8me et d'Organe H\u00f4pital Cochin, APHP. Centre Universit\u00e9 de Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude Brac","family":"de la Perri\u00e8re","sequence":"additional","affiliation":[{"name":"Service d'Endocrinologie, de Diab\u00e9tologie et des Maladies M\u00e9taboliques A Hospices Civiles de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Jonard\u2010Catteau","sequence":"additional","affiliation":[{"name":"D\u00e9partement d'Assistance M\u00e9dicale \u00e0 la Procr\u00e9ation H\u00f4pital Jeanne de Flandre  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Touraine","sequence":"additional","affiliation":[{"name":"D\u00e9partement d'Endocrinologie et M\u00e9decine de la Reproduction APHP. Sorbonne Universit\u00e9, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Center for Rare Endocrine and Gynecological Disorders, ERN\u2010HCP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Plu\u2010Bureau","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Gyn\u00e9cologie M\u00e9dicale APHP. Centre Universit\u00e9 Paris Cit\u00e9, H\u00f4pital Cochin  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Michel","family":"Dupont","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique des Maladies de Syst\u00e8me et d'Organe H\u00f4pital Cochin, APHP. Centre Universit\u00e9 de Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Christin\u2010Maitre","sequence":"additional","affiliation":[{"name":"Service d'endocrinologie, diab\u00e9tologie et M\u00e9decine de la Reproduction APHP. Sorbonne Universit\u00e9, H\u00f4pital Saint\u2010Antoine  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5953-2728","authenticated-orcid":false,"given":"Thierry","family":"Bienvenu","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique des Maladies de Syst\u00e8me et d'Organe H\u00f4pital Cochin, APHP. Centre Universit\u00e9 de Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000519836"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/84781"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.15.1591"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5771"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/346118"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/8.8.729"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh496"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gah078"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1472\u20106483(10)60388\u20104"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.065086"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016\u20102152"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13048\u2010020\u201000716\u20106"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13048\u2010023\u201001104\u20106"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010\u20100989"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.8.e43"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010023\u201002405\u20105"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14526","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:50:24Z","timestamp":1717375824000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14526"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":16,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1111\/cge.14526"],"URL":"https:\/\/doi.org\/10.1111\/cge.14526","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14526\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14526\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14526\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14526\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14526\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14526\/v1\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4]]},"assertion":[{"value":"2024-02-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}