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Hum. Reprod. Advance Access first published online on June 17, 2004
This version published online on June 30, 2004
Human Reproduction, doi:10.1093/humrep/deh342
© 2004 by European Society of Human Reproduction and Embryology
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Received January 8, 2004
Accepted May 6, 2004

Article

Mutational analysis of the mature peptide region of inhibin genes in Indian women with ovarian failure

H. Dixit 1, M. Deendayal 2, L. Singh 1*

1 Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, India
2 Infertility Institute and Research Centre, Hyderabad, India

* To whom correspondence should be addressed. E-mail: lalji{at}ccmb.res.in.


  Abstract

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: INH{beta}B and INH{beta}A genes do not show any association with ovarian failure. We found the Ala257Thr missense mutation in INH{alpha} 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 INH{alpha} gene is a strong candidate gene for ovarian failure. Mutations in INH{beta}B and INH{beta}A genes are not associated with ovarian failure.

Keywords: candidate gene; inhibin; mutation analysis; POF.
Lines 6 and and 10 of the abstract on page 1 of this article have been updated.
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