Abstract
Chromosomal rearrangements in Xq are frequently associated to premature ovarian failure (POF) and have contributed to define a POF “critical region” from Xq13.3 to Xq26. Search for X-linked genes responsible for the phenotype has been elusive as most rearrangements did not interrupt genes and many were mapped to gene deserts. We now report that ovary-expressed genes flanked autosomal breakpoints in four POF cases analyzed whose X chromosome breakpoints interrupted a gene poor region in Xq21, where no ovary-expressed candidate genes could be found. We also show that the global down regulation in the oocyte and up regulation in the ovary of X-linked genes compared to the autosomes is mainly due to genes in the POF “critical region”. We thus propose that POF, in X;autosome balanced translocations, may not only be caused by haploinsufficiency, but also by a oocyte-specific position effect on autosomal genes, dependent on dosage compensation mechanisms operating on the active X chromosome in mammals.
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Acknowledgments
We thank the patients and the colleagues that have provided the translocations cases: J. Gabarron (Murcia, Spain), J.P. Fryns (Leuven, Belgium), L. Larizza (Milano, Italy), G. Croci (Reggio Emilia, Italy) H. van Bokhoven (Nijmegen, The Netherlands). This work was supported by MIUR-FIRB RBNE0189HM_005 and Telethon Italy.
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Rizzolio, F., Sala, C., Alboresi, S. et al. Epigenetic control of the critical region for premature ovarian failure on autosomal genes translocated to the X chromosome: a hypothesis. Hum Genet 121, 441–450 (2007). https://doi.org/10.1007/s00439-007-0329-z
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DOI: https://doi.org/10.1007/s00439-007-0329-z