Confirmation of mosaicism and uniparental disomy in amniocytes, after detection of mosaic chromosome abnormalities in chorionic villi

Abstract

Chromosome mosaicism is detected in about 1-2% of chorionic villi samples (CVS), and may be due to a postzygotic nondisjunction event generating a trisomic cell line in an initially normal conceptus (mitotic origin) or the postzygotic loss of one chromosome in an initially trisomic conceptus (meiotic origin and trisomy rescue). Depending on the distribution of the abnormal cell line, the mosaic can be confined to the placenta (CPM) or generalised to the fetus (TFM, true fetal mosaicism). Trisomy rescue could theoretically be associated with a 33.3% probability of uniparental disomy (UPD) in the fetus. The aim of this study was to determine the risk of fetal involvement in a cohort of numerical and structural chromosome mosaics revealed in chorionic villi by means of combined direct and long-term culture analyses; we also determined the incidence of UPD associated with mosaic aneuploidies and supernumerary markers involving imprinted chromosomes. A total of 273 of a consecutive series of 15 109 CVS evaluated during a period of 5 years showed a mosaic condition in direct preparations and/or long-term cultures; confirmatory amniocentesis was performed in 203 cases. The abnormal cell line was extended to the fetus in 12.8% cases in terms of structural and numerical abnormalities involving autosomes and sex chromosomes; the risk of TFM varied and depended on the placental tissue distribution of the abnormal cell line. One of the 51 cases in which the mosaic involved an imprinted chromosome showed UPD, thus indicating a risk of 1.96%.

Cytogenetic confirmation of a positive NIPT result: evidence-based choice between chorionic villus sampling and amniocentesis depending on chromosome aberration

“…respectively, be trisomic or normal as well. Not only the older literature, but also recent papers that are not included in the database confirm this finding as well [21,29,30]. However, in 3.3% (23/704) of cases, LTC-villi revealed a mosaic trisomy, which requires follow-up investigations in amniotic fluid, since in about half of the cases (12/23) the trisomy will be confined to the placenta (Table 2).…”

A Retrospective and Theoretical Evaluation of Rapid Methods for Detecting Chromosome Abnormalities and Their Implications on Genetic Counseling Based on a Series of 3868 CVS Diagnoses

“…They can be minimized, but not completely avoided, by combining short-term culture of chorionic villi with long-term culture, which is time-consuming and delays the cytogenetic result by around weeks. According to the study performed by Grati et al [23] , only in 50% of true fetal mosaicisms did the longterm CVs culture show the real karyotype of the fetus. Furthermore, in 40% of the confined placental mosaicism long-term culture shows an abnormal result that is not confirmed in amniotic fluid, increasing the anxiety of the patient for a very long period of time.…”

Fetoplacental mosaicism: potential implications for false-positive and false-negative noninvasive prenatal screening results

“…14,15 In the direct preparation technique, metaphases were obtained "directly" from spontaneously dividing in vivo cytotrophoblasts using the protocol originally developed by Simoni et al in 1983. 16 Mesenchymal core analysis was performed on cultured cells, as previously described.…”