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Case Reports
. 2025 Jul 10;6(3):100443.
doi: 10.1016/j.xhgg.2025.100443. Epub 2025 Apr 21.

A variant in RNF212B may contribute to female infertility and recurrent pregnancy loss

Michelle E Darko  1 , Michelle Kappy  2 , Daniel Rabizadeh  3 , Chaim Jalas  4 , Eric J Forman  2 , Paula Brady  2 , Zev Williams  5
Affiliations
Case Reports

A variant in RNF212B may contribute to female infertility and recurrent pregnancy loss

Michelle E Darko et al. HGG Adv. .

Abstract

Women with genetic causes of infertility are more likely to experience recurrent pregnancy loss (RPL). Advances in whole-genome sequencing (WGS) have allowed for the improved detection of such genes. One reproductively young patient with a history of RPL underwent 5 in vitro fertilization cycles with nearly complete arrest of blastocyst development and ubiquitous aneuploidy of maternal origin in arrested embryos. Here, we present the discovery of a gene variant, RNF212B, as a potential genetic cause of female infertility and RPL. DNA was extracted and submitted for WGS. After filtering out variants with Genome Aggregation Database allele frequencies exceeding 0.25%, we identified 87 unique variants and conducted a literature search to identify potential associations with infertility. PGT-A analysis of arrested embryos revealed extensive aneuploidies affecting many chromosomes in all embryos. Maternal WGS revealed a homozygous stop-gain mutation in the RNF212B gene. RNF212 has been shown to interact with proteins involved in meiotic recombination, including DMC1 and DNA repair protein RAD51. This homozygous nonsense mutation in the RNF212B gene may be responsible for the presence of aberrant oogonium and for disrupting the meiotic recombination process, thereby contributing to female infertility and RPL.

Keywords: female infertility; genetics; recurrent pregnancy loss.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Figures

Figure 1
Figure 1
Arrested blastocyst trophectoderm biopsy analyzed by next-generation sequencing Trophectoderm biopsy of an arrested embryo revealed multiple aneuploidies (karyotype XXX+1,6,7,14,17,18) of maternal origin. Next-generation sequencing NGS testing was performed by Juno Genetics. (A) Karyotype aneuploidy: XY, −2, 4, 18, 20, −7, 8, 11, 21. (B) Karyotype triploidy: XX, 1, 10, 14, 15, mosaic (1, 10, 14, 15). (C) Karyotype aneuploidy: XX, +10, +18, segmental (2, 8), mosaic 6, 9, 17). (D) Karyotype triploidy: XX, +4, +8, +10, +14, +20, 1, 15, 17, 19, segmental 19, mosaic (1, 15, 17).
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References

    1. World Health Organization . World Health Organization; 2023. Infertility Prevalence Estimates, 1990–2021.https://www.who.int/publications/i/item/978920068315 Available at:
    1. Yatsenko S.A., Rajkovic A. Genetics of human female infertility. Biol. Reprod. 2019;101:549–566. doi: 10.1093/biolre/ioz084. - DOI - PMC - PubMed
    1. Zorrilla M., Yatsenko A.N. The Genetics of Infertility: Current Status of the Field. Curr. Genet. Med. Rep. 2013;1:247–260. doi: 10.1007/s40142-013-0027-1. - DOI - PMC - PubMed
    1. Dimitriadis E., Menkhorst E., Saito S., Kutteh W.H., Brosens J.J. Recurrent pregnancy loss. Nat. Rev. Dis. Primers. 2020;6:98. - PubMed
    1. Melo P., Dhillon-Smith R., Islam M.A., Devall A., Coomarasamy A. Genetic causes of sporadic and recurrent miscarriage. Fertil. Steril. 2023;120:940–944. doi: 10.1016/j.fertnstert.2023.08.952. - DOI - PubMed

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