Browsing by Author "Sahin, F.I."

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    Causative Mutations and Mechanism of Androgenetic Hydatidiform Moles
    (2018) Nguyen, N.M.P.; Ge, Z.-J.; Reddy, R.; Fahiminiya, S.; Sauthier, P.; Bagga, R.; Sahin, F.I.; Mahadevan, S.f; Osmond, M.; Breguet, M.; Rahimi, K.; Lapensee, L.; Hovanes, K.; Srinivasan, R.; Van den Veyver, I.B.; Sahoo, T.; Ao, A.; Majewski, J.; Taketo, T.; Sim, R.; 0000-0001-7308-9673; 30388401; AAC-7232-2020
    Androgenetic complete hydatidiform moles are human pregnancies with no embryos and affect 1 in every 1,400 pregnancies. They have mostly androgenetic monospermic genomes with all the chromosomes originating from a haploid sperm and no maternal chromosomes. Androgenetic complete hydatidiform moles were described in 1977, but how they occur has remained an open question. We identified bi-allelic deleterious mutations in MEI1, TOP6BL/C11orf80, and REC114, with roles in meiotic double-strand breaks formation in women with recurrent androgenetic complete hydatidiform moles. We investigated the occurrence of androgenesis in Mei1-deficient female mice and discovered that 8% of their oocytes lose all their chromosomes by extruding them with the spindles into the first polar body. We demonstrate that Mei1−/− oocytes are capable of fertilization and 5% produce androgenetic zygotes. Thus, we uncover a meiotic abnormality in mammals and a mechanism for the genesis of androgenetic zygotes that is the extrusion of all maternal chromosomes and their spindles into the first polar body. © 2018 American Society of Human Genetics