Identification of new variants of human BMP15 gene in a large cohort of women with premature ovarian failure

Elisa Di Pasquale, Raffaella Rossetti, Anna Marozzi, Beatrice Bodega, Stefano Borgato, Luciano Cavallo, Silvia Einaudi, Giorgio Radetti, Gianni Russo, Michele Sacco, Malgorzata Wasniewska, Trevor Cole, Paolo Beck-Peccoz, Lawrence M. Nelson, Luca Persani

Research output: Contribution to journalArticlepeer-review


Context: Premature ovarian failure (POF) is a cause of female infertility characterized by primary (PA) or secondary amenorrhea (SA) and elevated gonadotropins. The pathogenesis is unknown in most cases. We recently reported two sisters with PA carrying a heterozygous mutation of BMP15 gene (locus Xp11.2), but the prevalence of BMP15 variations in the POF population is unknown. Objective: The objective of the study was to verify the involvement of BMP15 variations in a large POF population. Design and Subjects: Genetic screening of 166 unrelated patients with idiopathic POF (25 PA, 141 SA) and controls (group A: 95 women with menopause beyond 50 yr of age; group B: 86 women and 30 men from the general population) of Caucasian origin. Results: Investigation revealed four heterozygous variations affecting the proregion of BMP15. The previously reported p.Y235C mutation occurred in one and three novel variants in eight patients: two missense alterations (p.R68W in one case, p.A180T in five) and one insertion (p.262insLeu) in two cases. The p.262insLeu was found in five controls of group A, thus diminishing its potential biological impact, whereas the other three variants were not present in any of the controls. All new mutations were found in SA cases. Conclusion: We describe the significant association of heterozygous BMP15 gene variants with the POF phenotype in humans (seven of 166 patients: 4.2%; P <0.003 vs. controls). These findings are consistent with the critical role played by BMP15 in human folliculogenesis.

Original languageEnglish
Pages (from-to)1976-1979
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Issue number5
Publication statusPublished - May 2006

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism


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