Genetics of Primary Ovarian Insufficiency

Abstract

Primary ovarian insufficiency (POI) is characterised by loss of ovarian function before the age of 40, and accounts for one major cause of female infertility. POI is highly heterogeneous in phenotype and aetiology. It has a strong genetic component, but aetiology in most cases remains idiopathic. Chromosomal abnormalities have long been recognised as a frequent cause of POI. On the basis of the candidate gene studies, single‐gene perturbations with a deleterious effect have been found in a few genes. Recent application in next‐generation sequencing (NGS) and whole‐exome approaches to familial POI have identified new causative genes responsible for POI. In the future, NGS studies will give more insight into the complex gene network involved in POI.

Key Concepts

  • Primary ovarian insufficiency (POI) is characterised by marked heterogeneity, but with a significant genetic contribution.
  • Chromosomal abnormalities, especially the X chromosome aberrations, have long been recognised as a frequent cause of POI.
  • No single underlying dominant gene deficiency could explain the disorder further supports the genetic heterogeneity of POI aetiology.
  • Family‐based whole‐exome and whole‐genome sequencing appear to be the most promising approaches for detecting potential genes responsible for POI.
  • Most genes identified by whole‐exome sequencing in POI pedigrees were involved in meiosis, DNA repair and chromosomal instability.

Keywords: primary ovarian insufficiency; premature ovarian failure; gene mutation; whole‐exome sequencing; next‐generation sequencing

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Jiao, Xue, and Chen, Zi‐Jiang(May 2018) Genetics of Primary Ovarian Insufficiency. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0026636]