X-chromosome inactivation (XCI) patterns in placental tissues of a paternally derived bal t(X;20) case

Non-random X-chromosome inactivation (XCI) is often seen in female carriers of balanced X-autosome translocations and is generally attributed to a selective growth of cells that inactivate the normal X chromosome. However, little is known concerning when in development the selection acts, and thus whether skewed XCI would also be seen in placental tissues. Furthermore, as males with X-autosome translocations are normally infertile, all translocations studied to date for XCI-skewing have been either maternal or de novo in origin. We now present an analysis of XCI status in cord blood, umbilical cord and four different extraembryonic tissues from a female carrier of a paternally derived balanced (X;20) translocation. Using methylation based assays to determine XCI status, we found preferential inactivation of the non-translocated X in cord blood, umbilical cord and amnion samples of the propositus. Remarkably, random XCI was evident in several placental tissues analyzed (chorion, and chorionic villi trophoblast and mesenchyme). While these findings support the hypothesis of strong selection against cells with an inactive translocated X-chromosome in most embryonic/fetal tissues, they also suggest weaker selective forces taking place during placental development. Additionally, the finding of normal placental development in the present case, rules out the possibility of a parental bias to XCI in human extraembryonic tissues as a requisite for normal development. The finding of hypomethylation in extraembryonic tissues for two out of three markers used in the study is consistent with previous findings demonstrating low levels of methylation in these tissues.