Journal of Assisted Reproduction and Genetics

, Volume 36, Issue 1, pp 39–45 | Cite as

Gene variants identified by whole-exome sequencing in 33 French women with premature ovarian insufficiency

  • Xiang Yang
  • Philippe Touraine
  • Swapna Desai
  • Gregory Humphreys
  • Huaiyang Jiang
  • Alexander Yatsenko
  • Aleksandar RajkovicEmail author



To investigate the potential genetic etiology of premature ovarian insufficiency (POI).


Whole-exome sequencing (WES) was done on DNA samples from women diagnosed with POI. Mutations identified were analyzed by in silico tools and were annotated according to the guidelines of the American College of Medical Genetics and Genomics. Plausible variants were confirmed by Sanger sequencing.


Four of the 33 individuals (12%) carried pathogenic or likely pathogenic variants, and 6 individuals carried variants of unknown significance. The genes identified with pathogenic or likely pathogenic variants included PMM2, MCM9, and PSMC3IP.


WES is an efficient tool for identifying gene variants in POI women; however, interpretation of variants is hampered by few exome studies involving ovarian disorders and the need for trio sequencing to determine inheritance and to detect de novo variants.


Premature ovarian insufficiency Whole-exome sequencing Gene variants 



We thank the affected individuals for their participation in this research study on the genetics of premature ovarian insufficiency. We thank the Magee Clinical Genomic Laboratory at Magee-Womens Hospital, UPMC (Pittsburgh, PA), for the whole-exome sequencing.


This research was funded by the National Institute of Child Health and Human Development (R01HD070647 and R21HD074278, A.R.).

Compliance with ethical standards

The study was approved by the Institutional Review Board of University of Pittsburgh (PRO09080427). Informed consent was obtained from all individual participants in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Xiang Yang
    • 1
    • 2
    • 3
  • Philippe Touraine
    • 4
    • 5
  • Swapna Desai
    • 1
  • Gregory Humphreys
    • 6
  • Huaiyang Jiang
    • 1
  • Alexander Yatsenko
    • 1
  • Aleksandar Rajkovic
    • 7
    • 8
    Email author
  1. 1.Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research InstituteUniversity of PittsburghPittsburghUSA
  2. 2.The Third Xiangya HospitalCentral South UniversityChangshaChina
  3. 3.Department of Gynecology, The Second Xiangya HospitalCentral South UniversityChangshaChina
  4. 4.Department of Endocrinology and Reproductive Medicine, Centre des Maladies Endocriniennes Rares de la Croissance et du DéveloppementCentre des Pathologies Gynécologiques RaresParisFrance
  5. 5.Pitie Salpetriere HospitalSorbonne UniversitéParisFrance
  6. 6.Magee-Womens HospitalPittsburghUSA
  7. 7.Department of PathologyUniversity of CaliforniaSan FranciscoUSA
  8. 8.Department of Obstetrics, Gynecology and Reproductive SciencesUniversity of CaliforniaSan FranciscoUSA

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