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Pathogenic missense variation in PABPC1L/EPAB causes female infertility due to oocyte maturation arrest at the germinal vesicle stage.
Okutman, O; Gürbüz, A S; Büyük, U; Real, E; Leconte, R; Chennen, K; Mayer, C; Muller, J; Le May, N; Viville, S.
Afiliación
  • Okutman O; Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B), Hôpital Erasme, Service de Gynécologie-Obstetrique, Clinique de Fertilité, Route de Lennik, 808, 1070, Brussels, Belgium.
  • Gürbüz AS; Novafertil IVF Center, Konya, Turkey.
  • Büyük U; Department of Molecular Biology and Genetics, Institute of Graduate Studies in Sciences, Istanbul University, Istanbul, Turkey.
  • Real E; Laboratoire de Génétique Médicale LGM, Institut de Génétique Médicale d'Alsace IGMA, INSERM UMR 1112, Université de Strasbourg, Strasbourg, France.
  • Leconte R; Laboratoire de Génétique Médicale LGM, Institut de Génétique Médicale d'Alsace IGMA, INSERM UMR 1112, Université de Strasbourg, Strasbourg, France.
  • Chennen K; Complex Systems and Translational Bioinformatics, ICube UMR 7357, Université de Strasbourg, 67000, Strasbourg, France.
  • Mayer C; Complex Systems and Translational Bioinformatics, ICube UMR 7357, Université de Strasbourg, 67000, Strasbourg, France.
  • Muller J; UFR Sciences de La Vie, Université Paris Cité, 75013, Paris, France.
  • Le May N; Laboratoire de Génétique Médicale LGM, Institut de Génétique Médicale d'Alsace IGMA, INSERM UMR 1112, Université de Strasbourg, Strasbourg, France.
  • Viville S; Unité Fonctionnelle de Bioinformatique Médicale Appliquée Au Diagnostic (UF7363), Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
J Assist Reprod Genet ; 41(2): 311-322, 2024 Feb.
Article en En | MEDLINE | ID: mdl-38177974
ABSTRACT
Women undergoing controlled ovarian hyperstimulation prior to in vitro fertilization (IVF) are treated using various protocols to induce multiple follicular growths. Complete failure of all oocytes to mature during IVF cycles is rare; however, it is a known cause of primary female infertility. Recently, pathogenic variations in a few genes have been identified in women with oocyte maturation defects; however, the underlying genetic causes remain largely unknown.This study included a Turkish family comprising three sisters with recurring oocyte maturation arrest at the germinal vesicle stage after multiple ovarian stimulations. Exome sequencing revealed a homozygous missense variant (c.1037C>T, p.Ala346Val) in the EPAB gene (also known as PABPC1L) in all three affected sisters, which was either absent or heterozygous in the unaffected family members. Functional experiments confirming the pathogenicity of the variant were performed by transfecting HEK293T cells and demonstrated the instability and increased rate of proteolysis of the mutated PABPC1L/EPAB protein. The identified variant, located in the well-conserved fourth RNA recognition motif (RRM4), in silico 3D modelling suggested changes in the physical properties of the pathogenic variant of PABPC1L/EPAB. Our findings validate PABPC1L/EPAB as an essential genetic contributor to the oocyte maturation process in humans and have direct implications for the genetic counselling of patients and their family members.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infertilidad Femenina Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Female / Humans Idioma: En Revista: J Assist Reprod Genet Asunto de la revista: GENETICA / MEDICINA REPRODUTIVA Año: 2024 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infertilidad Femenina Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Female / Humans Idioma: En Revista: J Assist Reprod Genet Asunto de la revista: GENETICA / MEDICINA REPRODUTIVA Año: 2024 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Países Bajos