Prenatal Diagnosis of Chromosomal Mosaicism in 18,369 Cases of Amniocentesis

Abstract

Objective The prenatal diagnosis of chromosomal mosaicism is fraught with uncertainty. Karyotyping, chromosomal microarray analysis (CMA), and fluorescence in situ hybridization (FISH) are three commonly used techniques. In this study, we evaluated these techniques for the prenatal diagnosis of chromosomal mosaicism and its clinical outcome. Study Design A retrospective review of mosaicism was conducted in 18,369 pregnant women from January 2016 to November 2021. The subjects underwent amniocentesis to obtain amniotic fluid for G-band karyotyping with or without CMA/FISH. Cases diagnosed with chromosomal mosaicism were selected for further analysis. Results In total, 101 cases of chromosomal mosaicism were detected in 100 pregnant women (0.54%, 100/18,369). Four were lost during follow-up, 61 opted to terminate their pregnancy, and 35 gave birth to a healthy singleton or twins. Among these 35 cases, postnatal cytogenetic testing was performed on eight and two exhibited mosaicism; however, nothing abnormal was observed in the postnatal phenotype follow-up. Karyotyping identified 96 incidents of chromosomal mosaicism including 13 with level II mosaicism and 83 with level III mosaicism, FISH identified 37 cases of mosaicism, and CMA identified 17. The most common form of chromosomal mosaicism involved monosomy X, of which the mosaic fraction in cultured karyotyping appeared higher or comparable to uncultured FISH/CMA (p < 0.05). Discordant mosaic results were observed in 34 of 101 cases (33.7%), most of which resulted from the detection limit of different techniques and/or the dominant growth of a certain cell line. Conclusion Based on the postnatal follow-up results from the babies born, we obtained a more hopeful result for the prognosis of chromosomal mosaicism. Although karyotyping was the most sensitive method for detecting chromosomal mosaicism, artifacts and bias resulting from culture should be considered, particularly for sex chromosomal abnormalities involving X monosomy, in which the combination with uncultured FISH was necessary. Key Points

The detection efficacy of noninvasive prenatal genetic testing (NIPT) for sex chromosome abnormalities and copy number variation and its differentiation in pregnant women of different ages

“…Amniocentesis or chromosome karyotype are currently the most used clinical approached for fetal chromosome abnormalities disgnosis, but both of these invasive procedures have the risk of consequences like fetal infection, fetal deformity, and abortion and cannot be widely used as screening tests [ 5 ]. It is reported that a total of 101 cases of chromosomal chimerism (0.54%, 100/18,369) are detected in 100 pregnant women, and it is concluded that although chromosome karyotype is the most sensitive method for detecting chromosomal chimera based on the results of postnatal follow-up of the infant at birth, culture-generated artifacts and biases should be considered, especially sex chromosome abnormalities involving X-monomer that require binding to uncultured fluorescence in situ hybridization [ 6 ]. The main prenatal screening method nowadays is clinical serological screening, with the advantages of rapid detection and inexpensive cost, but has poor detection rates and positive predictive values [ 7 ].…”