Background: Clinically, premature ovarian failure (POF) is defined as unexplained amenorrhoea (> 6 months) with a high FSH level (> 40 IU) before the age of 40 years. POF is a heterogeneous genetic disease with unknown aetiology. Inhibin and activin regulate the FSH level by their opposing actions and thus have been considered as strong candidate genes in the aetiology of POF.
Methods: We have screened inhibin genes in patients with POF (n = 80), primary amenorrhoea (n = 33) and secondary amenorrhoea (n = 4).
Results: INHbetaB and INHbetaA genes do not show any association with ovarian failure. We found the Ala257Thr missense mutation in INHalpha gene with high statistical significance in POF (nine out of 80, 11.2%) (Fisher's exact test, P = 0.0005), primary amenorrhoea (three out of 33, 9.1%) (Fisher's exact test, P = 0.014) and secondary amenorrhoea (two out of four, 50%) (Fisher's exact test, P = 0.001) with complete absence of this mutation in controls (none out of 100).
Conclusion: The INHalpha gene is a strong candidate gene for ovarian failure. Mutations in INHbetaB and INHbetaA genes are not associated with ovarian failure.
Copyright 2004 European Society of Human Reproduction and Embryology