A Human Homozygous HELQ Missense Variant Does Not Cause Premature Ovarian Insufficiency in a Mouse Model

Bakhshalizadeh, S; Bird, AD; Sreenivasan, R; Bell, KM; Robevska, G; van den Bergen, J; Asghari-Jafarabadi, M; Kueh, AJ; Touraine, P; Lokchine, A; Jaillard, S; Ayers, KL; Wilhelm, D; Sinclair, AH; Tucker, EJ

Author(s): Bakhshalizadeh, S; Bird, AD; Sreenivasan, R; Bell, KM; Robevska, G; van den Bergen, J; Asghari-Jafarabadi, M; Kueh, AJ; Touraine, P; Lokchine, A; Jaillard, S; Ayers, KL; Wilhelm, D; Sinclair, AH; Tucker, EJ;
Details: Publication Year 2024-03-04,Volume 15,Issue #3,Page 333
Journal Title: Genes
Abstract: Disruption of meiosis and DNA repair genes is associated with female fertility disorders like premature ovarian insufficiency (POI). In this study, we identified a homozygous missense variant in the HELQ gene (c.596 A>C; p.Gln199Pro) through whole exome sequencing in a POI patient, a condition associated with disrupted ovarian function and female infertility. HELQ, an enzyme involved in DNA repair, plays a crucial role in repairing DNA cross-links and has been linked to germ cell maintenance, fertility, and tumour suppression in mice. To explore the potential association of the HELQ variant with POI, we used CRISPR/Cas9 to create a knock-in mouse model harbouring the equivalent of the human HELQ variant identified in the POI patient. Surprisingly, Helq knock-in mice showed no discernible phenotype, with fertility levels, histological features, and follicle development similar to wild-type mice. Despite the lack of observable effects in mice, the potential role of HELQ in human fertility, especially in the context of POI, should not be dismissed. Larger studies encompassing diverse ethnic populations and alternative functional approaches will be necessary to further examine the role of HELQ in POI. Our results underscore the potential uncertainties associated with genomic variants and the limitations of in vivo animal modelling.
Publisher: MDPI
Keywords: Animals; Female; Humans; Mice; DNA Helicases/genetics; Homozygote; *Infertility, Female/genetics; Mutation, Missense; *Primary Ovarian Insufficiency/genetics; Helq; infertility; ovarian development; premature ovarian insufficiency
Research Division(s): Blood Cells And Blood Cancer
PubMed ID: 38540391
Publisher's Version: https://doi.org/10.3390/genes15030333
Open Access at Publisher's Site: https://doi.org/10.3390/genes15030333
Terms of Use/Rights Notice: Refer to copyright notice on published article.
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Creation Date: 2024-04-08 12:14:44

Last Modified: 2024-04-08 12:17:34