A pathogenic variant in the uncharacterized RNF212B gene results in severe aneuploidy male infertility and repeated IVF failure
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Le résumé fourni par la source
Quantitative and qualitative spermatogenic impairments are major causes of men’s infertility. Although in vitro fertilization (IVF) is effective, some couples persistently fail to conceive. To identify causal variants in patients with severe male infertility factor and repeated IVF failures, we sequenced the exome of two consanguineous family members who underwent several failed IVF cycles and were diagnosed with low sperm count and motility. We identified a rare homozygous nonsense mutation in a previously uncharacterized gene, RNF212B, as the causative variant. Recurrence was identified in another unrelated, infertile patient who also faced repeated failed IVF treatments. scRNA-seq demonstrated meiosis-specific expression of RNF212B. Sequence analysis located a protein domain known to be associated with aneuploidy, which can explain multiple IVF failures. Accordingly, FISH analysis revealed a high aneuploidy rate in the patients' sperm cells and their IVF embryos. Finally, inactivation of the Drosophila orthologs significantly reduced male fertility. Given that members of the evolutionary conserved RNF212 gene family are involved in meiotic recombination and crossover maturation, our findings indicate a critical role of RNF212B in meiosis, genome stability, and in human fertility. Since recombination is completely absent in Drosophila males, our findings may indicate an additional unrelated role for the RNF212-like paralogs in spermatogenesis.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- A pathogenic variant in the uncharacterized RNF212B gene results in severe aneuploidy male infertility and repeated IVF failure
- Date Crossref
- 01/07/2023
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Agricultural Research Organization pays non établi dans la noticeOrganisme public
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Weizmann Institute of Science Department of Molecular Genetics pays non établi dans la noticeUniversité ou école supérieure
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Tel Aviv University pays non établi dans la noticeUniversité ou école supérieure
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Tel Aviv Sourasky Medical Center pays non établi dans la noticeÉtablissement de santé
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ARO-The Volcani Center Institute of Animal Science pays non établi dans la noticeStructure de recherche
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affiliated with the Sackler Faculty of Medicine Racine IVF Unit and Male Fertility Clinic and Sperm Bank pays non établi dans la noticeUniversité ou école supérieure
Agricultural Research Organization, Department of Molecular Genetics — Weizmann Institute of Science et Tel Aviv University, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.