45,X/46,XX mosaicism below 30% of aneuploidy: clinical implications in adult women from a reproductive medicine unit

Abstract

Objective: Turner's syndrome (TS) is well known, but prognosis for 45,X/46,XX mosaicism below 30% of aneuploidy has not been established. We evaluated differences in clinical features and biological parameters between patients with numerical sex chromosome mosaicism diagnosed incidentally and control women. Design: Retrospective observational study of clinical features and biological parameters. Methods: Standard endocrinological and gynecological examination was done and early-follicularphase blood values were collected from the medical records of women aged 21-43, who were referred to our ward from 1996 to 2006 because of infertility and were karyotyped. Seventy-one women with sex chromosome mosaicism (45,X/46,XX) ranging from 4 to 28% were assigned a chromosomally normal woman (46,XX) matched according to age (nZ71). Results: In group 45,X/46,XX, 8% or more of aneuploidy accounted for a smaller height compared to controls (PZ0.01). Body mass index was increased from 6% of aneuploidy (PZ0.02) and was positively correlated to the percentage of 45,X cells (PZ0.0001); menarche occurred earlier from 10% of aneuploidy (PZ0.01) and was inversely correlated to the percentage of 45,X cells (PZ0.045). No difference was found between the groups for FSH, LH, estradiol, inhibin B, and TSH values. Spontaneous abortions were more frequent in case of mosaicism (PZ0.01), and recurrence was positively correlated to the percentage of aneuploidy (PZ0.008). Conclusion: Sex chromosome mosaicism is responsible for clinical changes from 6% of aneuploidy, corresponding to the main phenotypical features of TS.

Obstetric Outcomes in Women with Turner Karyotype

“…Karyotypes were subgrouped into four groups: 1) monosomy 45,X; 2) mosaics 45,X/46,XX; 3) others, including 45,X/46XY, 45,X/47,XXX, 45,X/48,XXXX, 45,X/49XXXXX 45,X/51,XXXXXX, and 45,X/46,Xder(X) (including ring chromosomes, deletions or translocations), isochromosomes 45,X/46,X,i(X) and 46,X,i(X); and 4) mosaics 45,X/46,XX with 45,X less than 6% (low-grade mosaics). The subgroup of mosaics with less than 6% 45,X cells was chosen because they probably represent healthier TS women with few or no stigmata (28).…”

Possible influence of menstrual cycle on lymphocyte X chromosome mosaicism

“…Although fluorescence in situ hybridization (FISH) may be the most appropriate method for detecting low level X chromosome mosaicism [9,14] we evaluated the presence of aneuploid metaphases by routine G-banding chromosome analysis, in order for the results to be comparable with some previous studies [5,6,12]. However, according to the International System for Human Cytogenetic Nomenclature (ISCN), numerical and structural abnormalities still have to be excluded at a banding level appropriate to the referral's guidelines [1,25,26].…”

“…Moreover, there is no consensus on the definition of what constitutes low level X mosaicism. Some authors consider it to be the presence of ≤10 % of aneuploid cells [4][5][6], others the presence of <6 % of aneuploid cells [7]. It can be found in women with premature ovarian failure, infertility or a history of recurrent pregnancy loss [4][5][6][8][9][10][11][12][13][14].…”

Chromosomal Abnormalities and Menstrual Cycle Disorders

“…For clinical changes to occur, a minimum of 6% of X chromosome aneuploidy is required [22,23]. "True" mosaicism represents the presence of more than 10% of aneuploid cells, whereas "low-level" mosaicism is defined as 6-10% of aneuploid cells.…”