BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency

"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 infertilit...

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Autores Principales: "Renault, Lucie, Patiño, Liliana C, Magnin, Françoise, Delemer, Brigitte, Young, Jacques, Laissue, Paul, Binart, Nadine, Beau, Isabelle"
Formato: Artículo (Article)
Lenguaje:Inglés (English)
Publicado: NLM (Medline) 2020
Materias:
Acceso en línea:https://repository.urosario.edu.co/handle/10336/23371
https://doi.org/10.1210/clinem/dgz226
id ir-10336-23371
recordtype dspace
spelling ir-10336-233712020-06-03T22:15:11Z BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency "Renault, Lucie Patiño, Liliana C Magnin, Françoise Delemer, Brigitte Young, Jacques Laissue, Paul Binart, Nadine Beau, Isabelle" Bone morphogenic protein receptor Follicular development Infertility "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." 2020 2020-05-26T00:01:28Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://repository.urosario.edu.co/handle/10336/23371 https://doi.org/10.1210/clinem/dgz226 eng info:eu-repo/semantics/openAccess application/pdf NLM (Medline) instname:Universidad del Rosario reponame:Repositorio Institucional EdocUR
institution EdocUR - Universidad del Rosario
collection DSpace
language Inglés (English)
topic Bone morphogenic protein receptor
Follicular development
Infertility
spellingShingle Bone morphogenic protein receptor
Follicular development
Infertility
"Renault, Lucie
Patiño, Liliana C
Magnin, Françoise
Delemer, Brigitte
Young, Jacques
Laissue, Paul
Binart, Nadine
Beau, Isabelle"
BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency
description "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."
format Artículo (Article)
author "Renault, Lucie
Patiño, Liliana C
Magnin, Françoise
Delemer, Brigitte
Young, Jacques
Laissue, Paul
Binart, Nadine
Beau, Isabelle"
author_facet "Renault, Lucie
Patiño, Liliana C
Magnin, Françoise
Delemer, Brigitte
Young, Jacques
Laissue, Paul
Binart, Nadine
Beau, Isabelle"
author_sort "Renault, Lucie
title BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency
title_short BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency
title_full BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency
title_fullStr BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency
title_full_unstemmed BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency
title_sort bmpr1a and bmpr1b missense mutations cause primary ovarian insufficiency
publisher NLM (Medline)
publishDate 2020
url https://repository.urosario.edu.co/handle/10336/23371
https://doi.org/10.1210/clinem/dgz226
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score 11,365685