Genes and translocations involved in POF

Am J Med Genet. 2002 Aug 15;111(3):328-33. doi: 10.1002/ajmg.10565.


Changes at a single autosomal locus and many X-linked loci have been implicated in women with gonadal dysgenesis [premature ovarian failure (POF) with deficits in ovarian follicles]. For the chromosome 3 locus, a forkhead transcription factor gene (FOXL2) has been identified, in which lesions result in decreased follicles by haploinsufficiency. In contrast, sporadic X; autosomal translocations are distributed at many points on the X, but concentrate in a critical region on Xq. The association of the breakpoints with genes involved in ovarian function is thus far weak (in four analyzed cases) and has not been related to pathology in other POF patients. While many more translocations can be analyzed in detail as the human genome sequence is refined, it remains possible that translocations like X monosomy (Turner syndrome) lead to POF not by interrupting specific genes important in ovarian development, but by causing aberrations in pairing or X-inactivation during folliculogenesis. It is noted that the critical region has unusual features, neighboring the X-inactivation center and including an 18 Mb region of very low recombination. These suggest that chromosome dynamics in the region may be sensitive to structural changes, and when modified by translocations might provoke apoptosis at meiotic checkpoints. Choices among models for the etiology of POF should be feasible based on studies of ovarian follicle development and attrition in mouse models. Studies would prominently include gene expression profiling of developmental-specific pathways in nascent ovaries with controlled levels of Foxl2 and interacting proteins, or with defined changes in the X chromosome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Chromosomes, Human, X
  • DNA-Binding Proteins / genetics
  • Female
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors
  • Genes, Dominant
  • Humans
  • Models, Genetic
  • Primary Ovarian Insufficiency / etiology
  • Primary Ovarian Insufficiency / genetics*
  • Sequence Deletion
  • Transcription Factors / genetics
  • Translocation, Genetic*


  • DNA-Binding Proteins
  • FOXL2 protein, human
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors
  • Transcription Factors