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Germline mutations in different genes are associated with premature ovarian failure (POF, OMIM 311360), defined as premature menopause with amenorrhea occurring before the age of 40 years along with increased gonadotropin concentrations [follicle-stimulating hormone (FSH) >40 IU/L]. A new candidate gene, bone morphogenetic protein 15 ( BMP15 ) has been investigated in POF. In a family affected by hypergonadotropic ovarian failure, a mutation in the pro-region of the BMP15 gene (Y235C) was found in 2 affected sisters (1), and 3 linked markers within the BMP15 gene (−673C>T, −9C>G and IVS1 + 905A>G) are associated with high follicle production in women undergoing recombinant FSH stimulation (2).Several heterozygous variations affecting the pro-region and mature peptide of the BMP15 gene have been identified in women with POF (3)(4)(5), but A180T was the only variant found in all reported studies, occurring with relatively high frequency in POF women (8 of 502, 1.6%) but not at all in control groups.To clarify the role of the A180T allele in early menopause and ovarian failure, we used a pyrosequencing protocol (Biotage) to evaluate the A180T …

Pyrosequencing Technology for Automated Detection of the BMP15 A180T Variant in Spanish Postmenopausal Women