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Other Original Articles: 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, and Luca Persani Identification of New Variants of Human BMP15 Gene in a Large Cohort of Women with Premature Ovarian Failure J Clin Endocrinol Metab 2006; 91: 1976-1979 [Abstract] [Full text] [PDF]

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The BMP15 mutation R68W, reported in familial ovarian failure, do not segregate with the phenotype

Reiner A. Veitia, Paul Laissue, Sophie Christin-Maitre, Marie-Christine Laurent   (22 March 2006)

The BMP15 mutation R68W, reported in familial ovarian failure, do not segregate with the phenotype 22 March 2006
Reiner A. Veitia, Professor of Genetics University Denis Diderot/Paris VII, Paul Laissue, Sophie Christin-Maitre, Marie-Christine Laurent Send letter to journal: Re: The BMP15 mutation R68W, reported in familial ovarian failure, do not segregate with the phenotype veitia{at}cochin.inserm.fr Reiner A. Veitia, et al.	We have read with great interest the article by Di Pasquale et al. (1) describing new BMP15 gene variants in a group of patients with premature ovarian failure (POF). We recently performed a similar screening of BMP15 and GDF9 variants in a large cohort of POF patients (2). In order to complement our studies, we have subsequently analyzed the BMP15 gene in a familial POF case. Interestingly, we found the same variant, 202C>T (R68W) at the heterozygous state, in the mother (without POF) and one affected daughter. However, the second POF daughter and the father did not carry the mutation. To confirm our results, we re-sequenced three independent PCR amplicons for each family member. Clinically, only one of the affected daughters had spontaneous breast development and both presented primary amenorrhea with FSH levels > 40 mUI/ml. The mother at the age of 49 was still taking the pill. We fully agree with the authors that mutation R68W involves a drastic amino acid change in terms of structure and polarity, in an evolutionarily conserved position. This logically suggests a causal association between the mutation and the ovarian phenotype. Nevertheless, in our familial case R68W cannot completely explain the ovarian phenotype. The involvement of two POF-inducing mutations in this family is possible but unlikely. Thus, although our results do not formally contradict those of Di Pasquale et al., they raise a question about the association between POF and this BMP15 variant. Since their familial case involves at least 9 infertile women, it would be interesting to analyze the segregation of the variant in that family to settle the issue. References 1. Di Pasquale E, Rossetti R, Marozzi A, Bodega B, Borgato S, Cavallo L,Einaudi S, Radetti G, Russo G, Sacco M, Wasniewska M, Cole T,Beck-Peccoz P, Nelson LM, and Persani L 2006 Identification of newvariants of human BMP15 gene in a large cohort of women with prematureovarian failure. J Clin Endocrinol Metab [2006 ; doi:10.1210/jc.2005-2650] 2. Laissue P, Christin-Maitre S, Touraine P, Kuttenn F, Ritvos O,Aittomaki K, Bourcigaux N, Jacquesson L, Bouchard P, Frydman R, DewaillyD , Reyss AC, Jeffery L, Bachelot A, Massin N, Fellous M, Veitia RA 2006Mutations and sequence variants in GDF9 and BMP15 in patients withpremature ovarian failure. Eur J Endocrinol (in press)