{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:36:10Z","timestamp":1790660170394,"version":"4.1.0"},"reference-count":12,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,3,30]],"date-time":"2017-03-30T00:00:00Z","timestamp":1490832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002738","name":"Assistance Publique - H\u00f4pitaux de Paris","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:p>Premature ovarian insufficiency (<jats:styled-content style=\"fixed-case\">POI<\/jats:styled-content>) affects 1% to 2% of women under 40\u2009years. Bone morphogenetic protein 15 (<jats:styled-content style=\"fixed-case\">BMP15<\/jats:styled-content>) variants have been described in <jats:styled-content style=\"fixed-case\">POI<\/jats:styled-content>. We studied a family with 2 sisters compound heterozygous for deletions in the <jats:styled-content style=\"fixed-case\">BMP15<\/jats:styled-content> gene on chromosome Xp11.22 yielding a human \u201cknockout\u2010like\u201d effect: a c.151_152delGA deletion yielded a p.<jats:styled-content style=\"fixed-case\">Glu51IlefsTer27<\/jats:styled-content> mutation transmitted by the hemizygous father and a c.189_198delAGGGCATTCAinsTG deletion\/insertion yielded a p.<jats:styled-content style=\"fixed-case\">Glu64AlafsTer12<\/jats:styled-content> mutation transmitted by the heterozygous mother. Both deletions resulted in frameshifts with premature stop codons at positions 78 and 76 in the proregion, precluding mature <jats:styled-content style=\"fixed-case\">BMP15<\/jats:styled-content> production. One sister had primary amenorrhea and the other primo\u2010secondary amenorrhea. No bone abnormality was observed. Despite streak ovaries devoid of follicles on ultrasonography, anti\u2010Mullerian hormone (<jats:styled-content style=\"fixed-case\">AMH<\/jats:styled-content>) levels were low but detectable suggesting the presence of growing follicles. Five years later, <jats:styled-content style=\"fixed-case\">AMH<\/jats:styled-content> was undetectable in both sisters, 1 had received an egg donation. <jats:styled-content style=\"fixed-case\">BMP15<\/jats:styled-content> did not seem critical for follicles to enter the growth phase. Genetic counselling should be performed and fertility preservation discussed before progressive loss of follicular reserve. The fertile heterozygous mother did not support previous reports of <jats:styled-content style=\"fixed-case\">BMP15<\/jats:styled-content> haploinsufficiency and gene dosage in humans, as in bovine species. The hemizygous brother had asthenozoospermia, consistent with previous observations in bulls with a variant <jats:styled-content style=\"fixed-case\">BMP15<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cge.12970","type":"journal-article","created":{"date-parts":[[2017,1,17]],"date-time":"2017-01-17T11:13:57Z","timestamp":1484651637000},"page":"208-212","source":"Crossref","is-referenced-by-count":31,"title":["BMP15 \u201cknockout\u2010like\u201d effect in familial premature ovarian insufficiency with persistent ovarian reserve"],"prefix":"10.1111","volume":"92","author":[{"given":"A.","family":"Mayer","sequence":"first","affiliation":[{"name":"Department of Endocrinology (AM) Chambery Hospital  Chambery France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Fouquet","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine Paris Sud Universit\u00e9 Paris Sud  Universit\u00e9 Paris Saclay, Le Kremlin Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Pugeat","sequence":"additional","affiliation":[{"name":"INSERM U1060 CARMEN Institute, F\u00e9d\u00e9ration d'endocrinologie Est (MP) Universit\u00e9 de Lyon 1  Oullins France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5379-8859","authenticated-orcid":false,"given":"M.","family":"Misrahi","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine Paris Sud Universit\u00e9 Paris Sud  Universit\u00e9 Paris Saclay, Le Kremlin Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,30]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmv036"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmu036"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.21265"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1312830110"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2837"},{"key":"e_1_2_5_7_1","first-page":"136","article-title":"What do semen parameters mean? How to define a normal semen analysis","volume":"4","author":"Chiles K","year":"2015","journal-title":"Andrology"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/422103"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deq073"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmp036"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1530\/rep.1.00529"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-1048"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.4238\/2014.March.17.8"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12970","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12970","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T05:20:37Z","timestamp":1694323237000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.12970"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,30]]},"references-count":12,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,8]]}},"alternative-id":["10.1111\/cge.12970"],"URL":"https:\/\/doi.org\/10.1111\/cge.12970","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,30]]}}}