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

J Assist Reprod Genet. 2019 Jan;36(1):39-45. doi: 10.1007/s10815-018-1349-4. Epub 2018 Nov 7.

Abstract

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

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Gene variants; Premature ovarian insufficiency; Whole-exome sequencing.

MeSH terms

  • Adult
  • Exome Sequencing / methods*
  • Exome*
  • Female
  • Genetic Variation*
  • Humans
  • Minichromosome Maintenance Proteins / genetics*
  • Nuclear Proteins / genetics*
  • Phosphotransferases (Phosphomutases) / genetics*
  • Primary Ovarian Insufficiency / genetics*
  • Primary Ovarian Insufficiency / pathology*
  • Trans-Activators / genetics*

Substances

  • Nuclear Proteins
  • PSMC3IP protein, human
  • Trans-Activators
  • MCM9 protein, human
  • Minichromosome Maintenance Proteins
  • Phosphotransferases (Phosphomutases)
  • phosphomannomutase 2, human