%0 Journal Article %T A recurrent ZP1 variant is responsible for oocyte maturation defect with degenerated oocytes in infertile females %+ Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB) %+ CHU Grenoble %+ Clinique de Promotion des Sciences de la Reproduction [Tunis] (CPSR) %+ Polyclinique les Jasmins [Tunis] %+ Modèles et Algorithmes pour la Génomique (TIMC-MAGe) %+ Centre Hospitalier Universitaire [Grenoble] (CHU) %A Loeuillet, Corinne %A Dhellemmes, Magali %A Cazin, Caroline %A Kherraf, Zine‐eddine %A Fourati Ben Mustapha, Selima %A Zouari, Raoudha %A Thierry‐mieg, Nicolas %A Arnoult, Christophe %A Ray, Pierre, F %< avec comité de lecture %@ 0009-9163 %J Clinical Genetics %I Wiley %V 102 %N 1 %P 22-29 %8 2022 %D 2022 %R 10.1111/cge.14144 %K infertility %K OMD %K oocytes %K zona pellucida %Z Life Sciences [q-bio]/Development Biology/GametogenesisJournal articles %X 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. %G English %2 https://cnrs.hal.science/hal-03720194/document %2 https://cnrs.hal.science/hal-03720194/file/loeuillet.ClinGenet22.pdf %L hal-03720194 %U https://cnrs.hal.science/hal-03720194 %~ INSERM %~ UGA %~ IMAG %~ CNRS %~ INPG %~ TIMC-IMAG %~ UNIV-LYON %~ UGA-EPE %~ TIMC-MAGE