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A recurrent ZP1 variant is responsible for oocyte maturation defect with degenerated oocytes in infertile females

Authors :
Corinne Loeuillet
Magali Dhellemmes
Caroline Cazin
Zine‐Eddine Kherraf
Selima Fourati Ben Mustapha
Raoudha Zouari
Nicolas Thierry‐Mieg
Christophe Arnoult
Pierre F. Ray
Thierry-Mieg, Nicolas
Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB)
Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
CHU Grenoble
Clinique de Promotion des Sciences de la Reproduction [Tunis] (CPSR)
Polyclinique les Jasmins [Tunis]
Modèles et Algorithmes pour la Génomique (TIMC-MAGe)
Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC )
VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )
Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )
Université Grenoble Alpes (UGA)
Centre Hospitalier Universitaire [Grenoble] (CHU)
Source :
Clinical Genetics, Clinical Genetics, 2022, 102 (1), pp.22-29. ⟨10.1111/cge.14144⟩
Publication Year :
2022
Publisher :
Wiley, 2022.

Abstract

International audience; A female factor is present in approximately 70% of couple infertility, often due to ovulatory disorders. In oocyte maturation defect (OMD), affected patients have a primary infertility with normal menstrual cycles but produce no oocyte, degenerated (atretic) or abnormal oocytes blocked at different stages of maturation. Four genes have so far been associated with OMD: PATL2, TUBB8, WEE2, and ZP1. In our initial study, 6 out of 23 OMD subjects were shown to carry the same PATL2 homozygous loss of function variant and one patient had a TUBB8 truncating variant. Here, we included four additional OMD patients and reanalyzed all 27 subjects. In addition to the seven patients with a previously identified defect, five carried the same deleterious homozygous ZP1 variant (c.1097G>A; p.Arg366Gln). All the oocytes from ZP1-associated patients appeared shriveled and dark indicating that the abnormal ZP1 protein induced oocyte death and degeneration. Overall ZP1-associated patients had degenerated or absent oocytes contrary to PATL2-associated subjects who had immature oocytes blocked mainly at the germinal vesicle stage. In this cohort of North African OMD patients, whole exome sequencing permitted to diagnose 44% of the patients studied and to identify a new frequent ZP1 variant.

Details

ISSN :
13990004 and 00099163
Volume :
102
Database :
OpenAIRE
Journal :
Clinical Genetics
Accession number :
edsair.doi.dedup.....9c759701fcd35b3c2dbc6bbffe2127ce
Full Text :
https://doi.org/10.1111/cge.14144