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Journal of Assisted Reproduction and Genetics

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01-10-2020 | Genetics

Novel variants in women with premature ovarian function decline identified via whole-exome sequencing

Authors: Ruiyi Tang, Qi Yu

Published in: Journal of Assisted Reproduction and Genetics | Issue 10/2020

Abstract

Purpose

To investigate the potential etiologies of premature ovarian insufficiency (POI) and diminished ovarian reserve (DOR).

Methods

Fourteen women with sporadic POI and 6 women with DOR were enrolled. We used whole-exome sequencing (WES) and bioinformatics analysis to identify variants in a subset of 599 selected POI candidate genes. The identified genes were subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and protein-protein interaction (PPI) network analyses to uncover key genes and pathways.

Results

Among the 20 patients, 79 heterozygous variants were detected in 49 genes, which were classified as “likely pathogenic” or “variants of uncertain significance” according to the guidelines of the American College of Medical Genetics and Genomics. Most patients (17/20) carried two or more variants. Monoacylglycerol O-acyltransferase 1 mutations were found in six patients, and cytochrome P450 family 26 subfamily B member 1 and Bardet-Biedl syndrome 9 mutations were each found in four patients. Some variants were shared between DOR and POI. Enrichment analyses showed that the identified genes participate in key ovarian processes, such as follicular development, gonadal development, meiosis, Fanconi anemia, homologous recombination, and transforming growth factor β signaling. A PPI network revealed interactions between these proteins.

Conclusion

Premature ovarian function decline may be polygenic, and overlap exists between the genetic backgrounds of DOR and POI. WES and in silico analyses may be a useful clinical tool for etiological diagnosis and risk prediction for high-risk women in the future.

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Title: Novel variants in women with premature ovarian function decline identified via whole-exome sequencing
Authors: Ruiyi Tang
Qi Yu
Publication date: 01-10-2020
Publisher: Springer US
Published in: Journal of Assisted Reproduction and Genetics / Issue 10/2020
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-020-01919-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Novel variants in women with premature ovarian function decline identified via whole-exome sequencing

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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