Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2012) 29 OC16.2

ICEECE2012 Oral Communications Female Reproduction Clinical (6 abstracts)

The first missense mutation of BMP15 mature domain identified in a Chinese family with primary ovarian insufficiency causes defective production of the bioactive protein

R. Rossetti 1, , E. Beccaria 1, & L. Persani 1,


1Università Statale di Milano, Milano, Italy; 2Istituto Auxologico Italiano IRCCS, Milano, Italy.


Primary Ovarian Insufficiency (POI) is an ovarian defect characterized by the premature depletion of ovarian follicles before 40 years and represents one major cause of female infertility. POI is a heterogeneous disease but, despite its idiopathic origin in most of patients, there is a strong genetic evidence, in particular for X chromosome-linked defects. BMP15 gene maps to Xp11.2 within a Turner locus critical for ovarian function and mutations in this gene have been found in the heterozygous state in association with both primary and secondary amenorrhea in several POI cohorts. All the variations are located in the proregion of the protein, except for the R329C substitution, identified very recently in the Chinese population, co-segragating with POI in mother and daughter, and is the first reported located in the mature peptide. Involving an Arg to Cys change, the mutation was predicted in silico to be possibly damaging by impairing the correct folding of the protein. To verify the in silico prediction, we further in vitro studied the mutation. By western blot analysis, we observed a reduced production of both precursor and mature peptide, moreover the mutant form showed a significant reduction of the BMP signalling pathway activity compared to the wild-type by a luciferase reporter assay in COV434 granulosa cells. We demontrated that the first mutation discovered in the BMP15 mature domain is responsible for an impairment of either the maturation process or the precursor stability, resulting in a defective secretion of the bioactive protein. This results suggest that the BMP15 haploinsufficiency could have caused the onset of POI in the Chinese family harbouring the R329C mutation. In conclusion, our analysis confirm the importance of the screening of BMP15 for the prediction of POI risk and the importance to evaluate functionally possible disease-linked mutations to be distinguished from rare polymorphisms.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

Browse other volumes

Article tools

My recent searches

No recent searches.