To assess the association between confined placental mosaicism (CPM) and adverse pregnancy outcome.
A retrospective cohort study was carried out evaluating the outcome of pregnancies with and without ...CPM involving a rare autosomal trisomy (RAT) or tetraploidy. Birthweight, gestational age at delivery, fetal growth restriction (FGR), Apgar score, neonatal intensive care admission, preterm delivery, and hypertensive disorders of pregnancy were considered.
Overall 181 pregnancies with CPM and 757 controls were recruited. Outcome information was available for 69% of cases (n = 124) and 62% of controls (n = 468). CPM involving trisomy 16 (T16) was associated with increased incidence of birthweight <3rd centile (P = 0.007, odds ratio OR = 11.2, 95% confidence interval CI = 2.7-47.1) and preterm delivery (P = 0.029, OR = 10.2, 95% CI = 1.9-54.7). For the other RATs, an association with prenatally diagnosed FGR was not supported by birthweight data and there were no other strong associations with adverse outcomes.
Excluding T16, the incidence of adverse pregnancy outcomes for pregnancies carrying a CPM is low. RATs can also be identified through genome-wide cell-free DNA screening. Because most of these will be attributable to CPMs, we conclude that this screening is of minimal benefit.
Chromosomal mosaicism in the fetoplacental unit Grati, Francesca Romana, BS, PhD, ErCLG; Malvestiti, Francesca, BS, ErCLG; Branca, Lara, BS ...
Best practice & research. Clinical obstetrics & gynaecology,
07/2017, Letnik:
42
Journal Article
Recenzirano
Abstract Cytogenetic prenatal diagnosis on chorionic villi (CV) can be complicated by the detection of a ‘chromosomal mosaicism’. This is one of the main issues of the first-trimester cytogenetic ...prenatal diagnosis as it can involve different types of chromosomal abnormalities and the prediction of the fetal involvement is challenging because the detected abnormal mosaic cell line is not necessarily extended to fetal tissues. In addition, because the cell-free fetal DNA that is targeted by the new technologies for fetal aneuploidies risk assessment is derived mainly from the CV cells, the same challenges related to chromosomal mosaicism can be shifted into this new clinical field. This review illustrates the phenomenon of the feto-placental mosaicism, the management of prenatal diagnosis cases complicated by the detection of such a biological phenomenon and the implications of its presence for the management of high risk cfDNA testing results for fetal aneuploidies.
The majority of human autoimmune diseases are characterized by female predominance. Although sex hormone influences have been suggested to explain this phenomenon, the mechanism remains unclear. In ...contrast to the role of hormones, it has been suggested, based on pilot data in primary biliary cirrhosis, that there is an elevation of monosomy X in autoimmune disease. Using peripheral white blood cells from women with systemic sclerosis (SSc), autoimmune thyroid disease (AITD), or healthy age-matched control women, we studied the presence of monosomy X rates using fluorescence in situ hybridization. We also performed dual-color fluorescence in situ hybridization analysis with a chromosome Y alpha-satellite probe to determine the presence of the Y chromosome in the monosomic cells. In subsets of patients and controls, we determined X monosomy rates in white blood cell subpopulations. The rates of monosomy X increased with age in all three populations. However, the rate of monosomy X was significantly higher in patients with SSc and AITD when compared with healthy women (6.2 +/- 0.3% and 4.3 +/- 0.3%, respectively, vs 2.9 +/- 0.2% in healthy women, p < 0.0001 in both comparisons). Importantly, X monosomy rate was more frequent in peripheral T and B lymphocytes than in the other blood cell populations, and there was no evidence for the presence of male fetal microchimerism. These data highlight the thesis that chromosome instability is common to women with SSc and AITD and that haploinsufficiency for X-linked genes may be a critical factor for the female predominance of autoimmune diseases.
In females, X chromosome inactivation (XCI) begins with the expression of the XIST gene from the X chromosome destined to be inactivated (Xi) and the coating of XIST RNA in cis. It has recently been ...reported that this process is supported by the product of the BRCA1 tumor suppressor gene and that BRCA1-/- cancers show Xi chromatin structure defects, thus suggesting a role of XCI perturbation in BRCA1-mediated tumorigenesis. Using a combined genetic and epigenetic approach, we verified the occurrence of XCI in BRCA1-/- and BRCA1wt breast cancer cell lines. It was ascertained that the Xi was lost in all cancer cell lines, irrespective of the BRCA1 status and that more than one active X (Xa) was present. In addition, no epigenetic silencing of genes normally subjected to XCI was observed. We also evaluated XIST expression and found that XIST may be occasionally transcribed also from Xa. Moreover, in one of the BRCA1wt cell line the restoring of XIST expression using a histone deacetylase inhibitor, did not lead to XCI. To verify these findings in primary tumors, chromosome X behavior was investigated in a few BRCA1-associated and BRCA1-not associated primary noncultured breast carcinomas and the results mirrored those obtained in cancer cell lines. Our findings indicate that the lack of XCI may be a frequent phenomenon in breast tumorigenesis, which occurs independently of BRCA1 status and XIST expression and is due to the loss of Xi and replication of Xa and not to the reactivation of the native Xi.
The aim of this study was to devise an evidence-based scoring system for prioritizing mosaic aneuploid embryos for transfer. A retrospective analysis was performed of all sequential cytogenetic and ...molecular results on chorionic villi samples (n = 72,472) and products of conception (n = 3806) analysed at a single centre. The likelihood that a mosaic aneuploidy detected in chorionic villi samples will involve the fetus, the incidence of clinically significant fetal uniparental disomy in the presence of a mosaic in chorionic villi and the chance of the mosaicism culminating in miscarriage were used to generate a scoring system for prioritizing mosaic aneuploid embryos detected by preimplantation genetic screening. A composite score was obtained for each individual mosaic aneuploidy after assignment of an individual risk score based on the incidence/likelihood of each adverse outcome. A final additional score was assigned to viable full or mosaic aneuploidies with a well-defined phenotype. The higher the composite score the lower the priority for embryo transfer. In conclusion, due to the paucity of prospective studies on the actual transfer of mosaic aneuploid embryos, we suggest using this evidence-based scoring system to provide a useful tool for clinicians, embryologists and patients.
Noninvasive prenatal screening for fetal aneuploidy analyzes cell-free fetal DNA circulating in the maternal plasma. Because cell-free fetal DNA is mainly of placental trophoblast origin, ...false-positive and false-negative findings may result from placental mosaicism. The aim of this study was to calculate the potential contribution of placental mosaicism in discordant results of noninvasive prenatal screening.
We performed a retrospective audit of 52,673 chorionic villus samples in which cytogenetic analysis of the cytotrophoblast (direct) and villus mesenchyme (culture) was performed, which was followed by confirmatory amniocentesis in chorionic villi mosaic cases. Using cases in which cytogenetic discordance between cytotrophoblast and amniotic fluid samples was identified, we calculated the potential contribution of cell line-specific mosaicism to false-positive and false-negative results of noninvasive prenatal screening.
The false-positive rate, secondary to the presence of abnormal cell line with common trisomies in cytotrophoblast and normal amniotic fluid, ranged from 1/1,065 to 1/3,931 at 10% and 100% mosaicism, respectively; the false-negative rate was calculated from cases of true fetal mosaicism, in which a mosaic cell line was absent in cytotrophoblast and present in the fetus; this occurred in 1/107 cases.
Despite exciting advances, underlying biologic mechanisms will never allow 100% sensitivity or specificity.
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