P-705 Homozygous missense variant in MEIOSIN causes premature ovarian insufficiency

نویسندگان

چکیده

Abstract Study question Are the gene variants involved in meiosis initiation responsible for premature ovarian insufficiency (POI)? Summary answer MEIOSIN variant participates pathogenesis of human POI by impairing due to insufficient transcriptional activation essential meiotic genes. What is known already Meiosis key event establishment reserve, and several defects homologous recombination have been found contribute POI. However, genes not associated with design, size, duration Retrospective genetic study. An in-house whole exome sequencing (WES) database 1,030 idiopathic patients was screened variations Participants/materials, setting, methods Gene were WES cases. The pathogenicity variation verified vitro experiments, including protein structure prediction dual-luciferase reporter assay. effect on function demonstrated through histological analyses a point mutation mouse model. Main results role chance A homozygous that initiates via retinoic acid dependent pathway identified patient assay revealed adversely affected upregulating Further knock-in mice confirmed impacted prophase I program accelerated oocyte depletion. Limitations, reasons caution studies are needed explore other Wider implications findings present study firstly pathogenic Although causative rare POI, our expanded spectrum elucidated different mechanisms infertility. Trial registration number Not available

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ژورنال

عنوان ژورنال: Human Reproduction

سال: 2023

ISSN: ['1460-2350', '0268-1161']

DOI: https://doi.org/10.1093/humrep/dead093.1027