Mutation analysis of two candidate genes for premature ovarian failure, DACH2 and POF1B.



Mutation analysis of two candidate genes for premature ovarian failure, DACH2 and POF1B

S.Bione, F.Rizzolio, C.Sala , R.Ricotti, M.Goegan , M.C.Manzini, R.Battaglia, A.Marozzi, W.Vegetti, L.Dalprà, P.G.Crosignani, E.Ginelli, R.Nappi, S.Bernabini,V.Bruni, F.Torricelli, O.Zuffardi and D.Toniolo.

Human Reproduction 19, 12: 2759-2766, 2004.

Background: Balanced X;autosome translocations interrupting the `critical region' of the long arm of the human X chromosome are often associated with premature ovarian failure (POF). However, the mechanisms lead¬ing to X-linked ovarian dysfunction are largely unknown, as the majority of the X chromosome breakpoints have been mapped to gene-free genomic regions. A few genes have been found to be interrupted, but their role has never been clarified. Methods and results: By fine mapping of the X chromosome breakpoint of an X;auto¬some balanced translocation, we identified a new interrupted gene, POFIB. We performed a mutation analysis of POFIB and of another gene previously identified, DACH2, localized -700kb distal in Xq21, in a cohort of >200 Italian POF patients. Rare mutations were found in patients in both genes. Conclusions: Our findings could not demonstrate any involvement of POF1B, but suggest that rare mutations in the DACH2 gene may have a role in the POE phenotype.