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


CONCLUSIONS
The INHalpha gene is a strong candidate gene for ovarian failure. Mutations in INHbetaB and INHbetaA genes are not associated with ovarian failure.
Dixit
H
H
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, India.
Deendayal
M
M
Singh
L
L
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007194:India; D028322:Inhibin-beta Subunits / Q000235:genetics*; D007265:Inhibins / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D016649:Primary Ovarian Insufficiency / Q000235:genetics*
C422402:INHBB protein, human; C103008:inhibin beta A subunit; C094377:inhibin-alpha subunit; D007265:Inhibins; D028322:Inhibin-beta Subunits