Apparent Neotelomere in a 46,X,del(X)(qter→p11.2:)/46,X,rea(X)(qter→p11.2::q21.2→qter) Novel Mosaicism: Review of 34 Females with a Recombinant-Like dup(Xq) Chromosome

Abstract

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.

De novo dup p/del q or dup q/del p Rearranged Chromosomes: Review of 104 Cases of a Distinct Chromosomal Mutation

“…In 3 patients (cases 23, 46, 104), the occurrence of a clone with the rec-like chromosome and another with a terminal deletion at the same or similar breakpoint, along with the absence of a euploid lineage, has been related to a meiotic origin of the former chromosome followed in the first or an early zygote cleavage by loss of the extra segment yielding a deleted chromosome stabilized by a neotelomere [Vasquez-Velásquez et al, 2011]. Mitotic instability appears to account for a concomitant 45,X or 47,X,rea(X),rea(X) clone in 10 patients, including 2 mothers who transmitted the rea(X) to a non-mosaic daughter (cases 80 and 100).…”

Chromosomal Abnormalities and Menstrual Cycle Disorders

“…Two main critical regions have been located on the long arm of X chromosome, at Xq13-q21 and at Xq26-q27 [25,26]. A few deletions in distal Xq have also been reported.…”