Causative Mutations and Mechanism of Androgenetic Hydatidiform Moles.
Am J Hum Genet
; 103(5): 740-751, 2018 11 01.
Article
em En
| MEDLINE
| ID: mdl-30388401
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mola Hidatiforme
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Androgênios
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Mutação
Limite:
Animals
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Female
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Humans
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Male
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Pregnancy
Idioma:
En
Revista:
Am J Hum Genet
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Canadá