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Whole-exome sequencing reveals new potential genes and variants in patients with premature ovarian insufficiency

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Premature ovarian insufficiency (POI) is a heterogeneous disorder characterized by the cessation of menstrual cycles before the age of 40 years due to the depletion or dysfunction of the ovarian follicles. POI is a highly heterogeneous disease in terms of etiology. The aim of this study is to reveal the genetic etiology in POI patients.

Methods

A total of 35 patients (mean age: 27.2 years) from 28 different families diagnosed with POI were included in the study. Karyotype, FMR1 premutation analysis, single nucleotide polymorphism (SNP) array, and whole-exome sequencing (WES) were conducted to determine the genetic etiology of patients.

Results

A total of 35 patients with POI were first evaluated by karyotype analysis, and chromosomal anomaly was detected in three (8.5%) and FMR1 premutation was detected in six patients (17%) from two different families. A total of 29 patients without FMR1 premutation were included in the SNP array analysis, and one patient had a 337-kb deletion in the chromosome 6q26 region including PARK2 gene, which was thought to be associated with POI. Twenty-nine cases included in SNP array analysis were evaluated simultaneously with WES analysis, and genetic variant was detected in 55.1% (16/29).

Conclusion

In the present study, rare novel variants were identified in genes known to be associated with POI, which contribute to the mutation spectrum. The effects of detected novel genes and variations on different pathways such as gonadal development, meiosis and DNA repair, or metabolism need to be investigated by experimental studies. Molecular etiology allows accurate genetic counseling to the patient and family as well as fertility planning.

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Acknowledgements

We sincerely thank all the patients and their family members for donating their biological samples.

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Authors and Affiliations

  1. Department of Medical Genetics, School of Medicine, Karadeniz Technical University, Trabzon, Turkey

    Ayberk Turkyilmaz, Mehmet Gokcu & Alper Han Cebi

  2. Department of Medical Genetics, School of Medicine, Marmara University, Istanbul, Turkey

    Ceren Alavanda, Bilgen Bilge Geckinli, Hamza Polat, Mehmet Ali Soylemez, Ahmet İlter Guney, Pinar Ata & Ahmet Arman

  3. Department of Medical Genetics, Marmara University Pendik Training and Research Hospital, Istanbul, Turkey

    Esra Arslan Ates

  4. Department of Medical Genetics, Isparta City Hospital, Isparta, Turkey

    Taner Karakaya

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  1. Ayberk Turkyilmaz
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Contributions

Conceptualization: Ayberk Turkyilmaz; Methodology: Ayberk Turkyilmaz; Formal analysis and investigation: Ceren Alavanda, Esra Arslan Ates, Bilgen Bilge Geckinli, Hamza Polat, Taner Karakaya, Mehmet Gokcu, Alper Han Cebi; Writing—original draft preparation: Ayberk Turkyilmaz; Writing—review and editing: Mehmet Ali Soylemez, Ahmet Ilter Guney, Pinar Ata, Ahmet Arman; Supervision: Ahmet İlter Guney, Pinar Ata, Ahmet Arman.

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Correspondence to Ayberk Turkyilmaz.

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Turkyilmaz, A., Alavanda, C., Ates, E.A. et al. Whole-exome sequencing reveals new potential genes and variants in patients with premature ovarian insufficiency. J Assist Reprod Genet 39, 695–710 (2022). https://doi.org/10.1007/s10815-022-02408-0

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  • DOI: https://doi.org/10.1007/s10815-022-02408-0

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