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Analysis of NR5A1 in 142 patients with premature ovarian insufficiency, diminished ovarian reserve, or unexplained infertility.
Jaillard, Sylvie; Sreenivasan, Rajini; Beaumont, Marion; Robevska, Gorjana; Dubourg, Christèle; Knarston, Ingrid M; Akloul, Linda; van den Bergen, Jocelyn; Odent, Sylvie; Croft, Brittany; Jouve, Guilhem; Grover, Sonia R; Duros, Solène; Pimentel, Céline; Belaud-Rotureau, Marc-Antoine; Ayers, Katie L; Ravel, Célia; Tucker, Elena J; Sinclair, Andrew H.
Afiliación
  • Jaillard S; Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, 3052, Australia; Univ Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France; CHU Rennes, Service de Cytogénétique et Biologie Cellulai
  • Sreenivasan R; Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, 3052, Australia.
  • Beaumont M; CHU Rennes, Service de Cytogénétique et Biologie Cellulaire, F-35033, Rennes, France.
  • Robevska G; Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, 3052, Australia.
  • Dubourg C; CHU Rennes, Service de Génétique Moléculaire, F-35033, Rennes, France.
  • Knarston IM; Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, 3052, Australia.
  • Akloul L; CHU Rennes, Service de Génétique Clinique, CLAD Ouest, F-35033, Rennes, France.
  • van den Bergen J; Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, 3052, Australia.
  • Odent S; CHU Rennes, Service de Génétique Clinique, CLAD Ouest, F-35033, Rennes, France.
  • Croft B; Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, 3052, Australia.
  • Jouve G; CHU Rennes, Service de Biologie de la Reproduction, F-35033, Rennes, France.
  • Grover SR; Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, 3052, Australia; Department of Paediatric and Adolescent Gynaecology, Royal Children's Hospital, Melbourne, VIC, 3052, Australia.
  • Duros S; CHU Rennes, Département de Gynécologie Obstétrique et Reproduction Humaine, F-35033, Rennes, France.
  • Pimentel C; CHU Rennes, Département de Gynécologie Obstétrique et Reproduction Humaine, F-35033, Rennes, France.
  • Belaud-Rotureau MA; Univ Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France; CHU Rennes, Service de Cytogénétique et Biologie Cellulaire, F-35033, Rennes, France; CHU Rennes, Service de Biologie de la Reproduction, F-35033, Rennes, F
  • Ayers KL; Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, 3052, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, 3052, Australia.
  • Ravel C; Univ Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France; CHU Rennes, Service de Biologie de la Reproduction, F-35033, Rennes, France.
  • Tucker EJ; Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, 3052, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, 3052, Australia.
  • Sinclair AH; Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, 3052, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, 3052, Australia.
Maturitas ; 131: 78-86, 2020 Jan.
Article en En | MEDLINE | ID: mdl-31787151
Ovarian deficiency, including diminished ovarian reserve and premature ovarian insufficiency, represents one of the main causes of female infertility. Little is known of the genetic basis of diminished ovarian reserve, while premature ovarian insufficiency often has a genetic basis, with genes affecting various processes. NR5A1 is a key gene required for gonadal function, and variants are associated with a wide phenotypic spectrum of disorders of sexual development, and are found in 0.26-8% of patients with premature ovarian insufficiency. As there is some debate about the extent of involvement of NR5A1 in the pathogenesis of ovarian deficiency, we performed an in-depth analysis of NR5A1 variants detected in a cohort of 142 patients with premature ovarian insufficiency, diminished ovarian reserve, or unexplained infertility associated with normal ovarian function. We identified rare non-synonymous protein-altering variants in 2.8 % of women with ovarian deficiency and no such variants in our small cohort of women with infertility but normal ovarian function. We observed previously reported variants associated with premature ovarian insufficiency in patients with diminished ovarian reserve, highlighting a genetic relationship between these conditions. We confirmed functional impairment resulting from a p.Val15Met variant, detected for the first time in a patient with premature ovarian insufficiency. The remaining variants were associated with preserved transcriptional activity and localization of NR5A1, indicating that rare NR5A1 variants may be incorrectly curated if functional studies are not undertaken, and/or that NR5A1 variants may have only a subtle impact on protein function and/or confer risk of ovarian deficiency via oligogenic inheritance.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Menopausia Prematura / Insuficiencia Ovárica Primaria / Factor Esteroidogénico 1 / Reserva Ovárica / Infertilidad Femenina Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans Idioma: En Revista: Maturitas Año: 2020 Tipo del documento: Article Pais de publicación: Irlanda
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Menopausia Prematura / Insuficiencia Ovárica Primaria / Factor Esteroidogénico 1 / Reserva Ovárica / Infertilidad Femenina Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans Idioma: En Revista: Maturitas Año: 2020 Tipo del documento: Article Pais de publicación: Irlanda