Genetic Testing and Molecular Biomarkers

A 26-year-old woman with secondary amenorrhea and turneroid stigmata was found to have a 46,X,rea(X)(qter→p11.2::q21.2→qter)/46,X,del(X)(qter→p11.2:) mosaicism in 101 G-banded metaphases (71 and 30, respectively). The mother's karyotype was normal (the father was already deceased). A fully skewed inactivation of both abnormal X-chromosomes was documented in RBG-banded metaphases and by means of the HUMARA assay. In addition, the latter revealed that the involved X-chromosome was the paternal one. The patient's secondary amenorrhea and turneroid stigmata can reliably be ascribed to her nearly complete Xp deletion present in all cells. Thus, this observation is consistent with the well-known gradation of ovarian function depending on the Xp deletion size. We assume that the first event was an intrachromosome recombination during paternal meiosis between paralogous sequences at Xp11.2 and Xq21.2, which resulted in a fertilizing rea(X) spermatozoid. Early in embryogenesis, the rea(X) dissociated at the Xp11.2 junction point to originate the del(X), which in turn was healed by the de novo addition of telomeric repeats (the acentric Xq21.2→qter segment was lost in the process). The reverse sequence appears unlikely because it implies that the del(X) chromosome was healed only after it undergone a postzygotic interchromatid recombination and apposite segregation required to obtain the rea(X) clone. The present observation further expands the cytogenetic heterogeneity in Turner syndrome and may represent another instance of a terminal deletion healed by the de novo addition of telomeric repeats.