ABSTRACT: Premature ovarian failure (POF) is unexplained amenorrhoea (>6 months), increased FSH (>20 IU/l) and LH occurring before 40 years. Several genes are reported as having significance in POF, including genes governing regulation of the hypothalamic-pituitary-ovarian axis, but their role in ovarian physiology is not known. Deletions or translocations in Xq arm have been found to be associated with POF, assuming presence of ovarian-related genes but ovary-related function of these genes is unclear. Several researchers have suggested specific loci on Xq critical region, POF1 and POF2 and genes DIA, FMR1 and FMR2. The understanding of ovarian physiology, its regulation and genes involved is important to explain the causes of POF. Some genes coordinate development of germ cell to primordial stage, e.g. GDF9, BMP15 and NGF, while others regulate development of further stages, such as FSH and LH. Mutation in these genes may lead to female infertility and are likely to be candidate genes for POF. Recently, association between blepharophimosis-ptosis-epicanthus inversus syndrome type 1 and POF has emerged as a possibility. Galactosaemia is also shown to be important in POF due to toxic effects of accumulated galactose or downstream products. Thus, understanding the role of several genes can be used for the appropriate genetic diagnosis, research and in the clinical practice of POF.
Reproductive biomedicine online 03/2010; 20(6):724-40. · 2.04 Impact Factor