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BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency
| dc.creator | Renault, Lucie | spa |
| dc.creator | Patiño, Liliana C | spa |
| dc.creator | Magnin, Françoise | spa |
| dc.creator | Delemer, Brigitte | spa |
| dc.creator | Young, Jacques | spa |
| dc.creator | Laissue, Paul | spa |
| dc.creator | Binart, Nadine | spa |
| dc.creator | Beau, Isabelle | spa |
| dc.date.accessioned | 2020-05-26T00:01:28Z | |
| dc.date.available | 2020-05-26T00:01:28Z | |
| dc.date.created | 2020 | spa |
| dc.description.abstract | CONTEXT: Primary ovarian insufficiency (POI) is a frequently occurring disorder affecting approximately 1% of women under 40 years of age. POI, which is characterized by the premature depletion of ovarian follicles and elevated plasma levels of follicle-stimulating hormone, leads to infertility. Although various etiological factors have been described, including chromosomal abnormalities and gene mutations, most cases remain idiopathic. OBJECTIVE: To identify and to functionally validate new sequence variants in 2 genes that play a key role in mammalian ovarian function, BMPR1A and BMPR1B (encoding for bone morphogenic protein receptor), leading to POI. METHODS: The impact on bone morphogenic protein (BMP) signaling of BMPR1A and BMPR1B variants, previously identified by whole-exome sequencing on 69 women affected by isolated POI, was established by different in vitro functional experiments. RESULTS: We demonstrate that the BMPR1A-p.Arg442His and BMPR1B-p.Phe272Leu variants are correctly expressed and located but lead to an impairment of downstream BMP signaling. CONCLUSION: In accordance with infertility observed in mice lacking Bmpr1a in the ovaries and in Bmpr1b-/- mice, our results unveil, for the first time, a link between BMPR1A and BMPR1B variants and the origin of POI. We show that BMP signaling impairment through specific BMPR1A and BMPR1B variants is a novel pathophysiological mechanism involved in human POI. We consider that BMPR1A and BMPR1B variants constitute genetic biomarkers of the origin of POI and have clinical utility. © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. | eng |
| dc.format.mimetype | application/pdf | |
| dc.identifier.doi | https://doi.org/10.1210/clinem/dgz226 | |
| dc.identifier.uri | https://repository.urosario.edu.co/handle/10336/23371 | |
| dc.language.iso | eng | spa |
| dc.publisher | NLM (Medline) | spa |
| dc.relation.citationIssue | No. 4 | |
| dc.relation.citationTitle | The Journal of clinical endocrinology and metabolism | |
| dc.relation.citationVolume | Vol. 105 | |
| dc.relation.ispartof | The Journal of clinical endocrinology and metabolism, Vol.105, No.4 (2020) | spa |
| dc.relation.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85081945965&doi=10.1210%2fclinem%2fdgz226&partnerID=40&md5=5db06b813c1defcea2896860b266c1ad | spa |
| dc.rights.accesRights | info:eu-repo/semantics/openAccess | |
| dc.rights.acceso | Abierto (Texto Completo) | spa |
| dc.source.instname | instname:Universidad del Rosario | spa |
| dc.source.reponame | reponame:Repositorio Institucional EdocUR | spa |
| dc.subject.keyword | Bone morphogenic protein receptor | spa |
| dc.subject.keyword | Follicular development | spa |
| dc.subject.keyword | Infertility | spa |
| dc.title | BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency | spa |
| dc.type | article | eng |
| dc.type.hasVersion | info:eu-repo/semantics/publishedVersion | |
| dc.type.spa | Artículo | spa |
