Low-level X chromosome mosaicism in women with sporadic premature ovarian failure

Abstract

Low-level X chromosome mosaicism and its clinical relevance are still under debate. It could be interpreted as a technical artefact, genuine mosaicism or as being age-related. This study evaluated the contribution of X chromosome mosaicism in phenotypically normal women with sporadic premature ovarian failure (POF). During 1999-2008, 114 patients with POF and 64 age matched controls were karyotyped. Thirteen patients (11.4%) had true X chromosome mosaicism (>10% of aneuploid cells) and 12 had (10.5%) low-level X-mosaicism (between 6-10% of aneuploid cells). The mean age of women with true and low-level mosaicism was 26.0 ± 5.65 years and 35.92 ± 3.87 years, respectively (P < 0.001). In the control group the incidence of cells with an abnormal number of X chromosomes was 1-3%. The results have practical implications for genetic counselling and fertility treatment. To search and confirm the low-level mosaicism, a higher number of metaphases should be analysed or additional fluorescence in-situ hybridization analysis must be performed. Although peripheral blood does not reflect the situation in ovarian tissue well, it is presumed that there are different aetiological causes for true and low-level X chromosome mosaicism. The possible causes and reproductive significance of low-level X chromosome mosaicism are discussed.

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].…”

“…The presence of more than 10 % of aneuploid cells was considered true level X mosaicism, whereas low level X mosaicism was defined as 6-10 % of aneuploid cells [6]. X chromosome mosaic state was excluded when less than 5 % of aneuploid cells were present in blood samples from both the follicular and luteal phases.…”

“…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.…”

“…"True" mosaicism represents the presence of more than 10% of aneuploid cells, whereas "low-level" mosaicism is defined as 6-10% of aneuploid cells. The frequency of X chromosome mosaicism in women with sporadic form of POI has been estimated to be between 3 and 21% [23]. Upon comparison between patients with X-chromosome mosaicism and those with a balanced structural autosomal rearrangement, patients with X-chromosome mosaicism have a significantly higher incidence of diminished ovarian reserve [24].…”