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Identification of new variants and candidate genes in women with familial premature ovarian insufficiency using whole-exome sequencing

  • Genetics
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Abstract 

Purpose

To identify candidate variants in genes possibly associated with premature ovarian insufficiency (POI).

Methods

Fourteen women, from 7 families, affected by idiopathic POI were included. Additionally, 98 oocyte donors of the same ethnicity were enrolled as a control group. Whole-exome sequencing (WES) was performed in 14 women with POI to identify possibly pathogenic variants in genes potentially associated with the ovarian function. The candidate genes selected in POI patients were analysed within the exome results of oocyte donors.

Results

After the variant filtering in the WES analysis of 7 POI families, 23 possibly damaging genetic variants were identified in 22 genes related to POI or linked to ovarian physiology. All variants were heterozygous and five of the seven families carried two or more variants in different genes. We have described genes that have never been associated to POI pathology; however, they are involved in important biological processes for ovarian function. In the 98 oocyte donors of the control group, we found no potentially pathogenic variants among the 22 candidate genes.

Conclusion

WES has previously shown as an efficient tool to identify causative genes for ovarian failure. Although some studies have focused on it, and many genes are identified, this study proposes new candidate genes and variants, having potentially moderate/strong functional effects, associated with POI, and argues for a polygenic etiology of POI in some cases.

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Acknowledgements

The authors would like to thank Ania Pitas for the revision and correction of the language.

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Authors and Affiliations

  1. Molecular Biology, Instituto Bernabeu, 03016, Alicante, Spain

    R. Morales, B. Lledo, J. A. Ortiz, F. M. Lozano & E. M. Garcia

  2. Reproductive Medicine, Instituto Bernabeu, 03016, Alicante, Spain

    A. Bernabeu, A. Fuentes & R. Bernabeu

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  1. R. Morales
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  2. B. Lledo
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  3. J. A. Ortiz
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Morales, R., Lledo, B., Ortiz, J.A. et al. Identification of new variants and candidate genes in women with familial premature ovarian insufficiency using whole-exome sequencing. J Assist Reprod Genet 39, 2595–2605 (2022). https://doi.org/10.1007/s10815-022-02629-3

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