- Human pathology

Home > E. Pathology by systems > Reproductive system > Female genital system > Ovaries (Ovary) > ovarian failure

ovarian failure

Friday 26 September 2003


Ovarian failure can result from several different genetic mechanisms: X chromosomal abnormalities, autosomal recessive genes causing various types of XX gonadal dysgenesis, and autosomal dominant genes.

The number and precise location of loci on the X are still under investigation, but it is clear that, in aggregate, these genes are responsible for ovarian maintenance, given that monosomy X shows germ cells that undergo accelerated atresia.

There is no evidence for a gene directing primary ovarian differentiation; this process may be constitutive.

Phenotypic/karyotypic correlation and limited molecular confirmation have long shown that proximal Xp and proximal Xq contain regions of the most importance to ovarian maintenance.

Terminal deletions at Xp11 result in 50% primary amenorrhea and 50% premature ovarian failure or fertility.

Deletions at Xq13 usually produce primary amenorrhea.

Terminal deletions nearer the telomeres on either Xp of Xq bring about premature ovarian failure more often than complete ovarian failure.

The X-linked zinc finger gene (ZFX) and diaphanous 2 Drosophila homologue (DIAPH2) are the only candidate genes for ovarian maintenance that map to the X chromosome.

Autosomal genes also are involved in ovarian differentiation and gonadal failure. Follicle-stimulating hormone receptor and ataxia telangiectasia are examples of autosomal genes known to cause human ovarian failure.


- mutations in three of the five EIF2B genes (EIF2B2, -4, and -5) coding for eukaryotic initiation factor 2B (12707859)

- NOBOX homeobox mutation causes premature ovarian failure. (17701902)

  • NOBOX (newborn ovary homeobox gene) is an oocyte-specific homeobox gene that plays a critical role in early folliculogenesis and represents a candidate gene for nonsyndromic ovarian failure.
  • NOBOX is a homeobox gene that is preferentially expressed in oocytes. In mice, NOBOX is essential for folliculogenesis and regulation of oocyte-specific genes.


- Qin Y, Choi Y, Zhao H, Simpson JL, Chen ZJ, Rajkovic A. NOBOX homeobox mutation causes premature ovarian failure. Am J Hum Genet. 2007 Sep;81(3):576-81. PMID: 17701902

- Simpson JL, Rajkovic A. Ovarian differentiation and gonadal failure. Am J Med Genet. 1999 Dec 29;89(4):186-200. PMID: 10727994