Search

Background: Emerging studies suggest that low-coverage massively parallel copy number variation sequencing (CNV-seq) more sensitive than chromosomal microarray analysis (CMA) for detecting low-level mosaicism. However, a retrospective back-to-back comparison evaluating accuracy, efficacy, and incremental yield of CNV-seq compared with CMA is warranted., Methods: A total of 72 mosaicism cases identified by karyotyping or CMA were recruited to the study. There were 67 mosaic samples co-analysed by CMA and CNV-seq, comprising 40 with sex chromosome aneuploidy, 22 with autosomal aneuploidy and 5 with large cryptic genomic rearrangements., Results: Of the 67 positive mosaic cases, the levels of mosaicism defined by CNV-seq ranged from 6 to 92% compared to the ratio from 3 to 90% by karyotyping and 20% to 72% by CMA. CNV-seq not only identified all 43 chromosomal aneuploidies or large cryptic genomic rearrangements detected by CMA, but also provided a 34.88% (15/43) increased yield compared with CMA. The improved yield of mosaicism detection by CNV-seq was largely due to the ability to detect low level mosaicism below 20%., Conclusion: In the context of prenatal diagnosis, CNV-seq identified additional and clinically significant mosaicism with enhanced resolution and increased sensitivity. This study provides strong evidence for applying CNV-seq as an alternative to CMA for detection of aneuploidy and mosaic variants.

Objective: To explore the prenatal screening and diagnosis for a pair of monochorionic-diamniotic (MCDA) twins discordant for 45,X/46,XX mosaicism., Methods: Amniotic fluid samples were taken from both twins for whom non-invasive prenatal testing has signaled a high risk for sex chromosomal abnormality. Uncultured amniotic fluid was analyzed by fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array (SNP-array). Conventional G-banded karyotyping analysis was performed on the cultured amniotic fluid., Results: Metaphase chromosome analysis showed that one of the twins had a mos 45,X[11]/46,XX[26] karyotype, while the other had a normal karyotype. FISH and SNP-array applied on uncultured amniotic fluid revealed about 30% mosaicism in one of the twins. The twins were confirmed to be monozygotic by SNP-array analysis., Conclusion: To avoid confusion arising from discordant karyotypes in MCDA twins with abnormal non-invasive prenatal testing (NIPT) results, dual amniocentesis should be carried out to obtain amniotic fluid samples for chromosomal as well as molecular analysis. To determine the ratio of 45,X and 46,XX cells in Turner syndrome can provide valuable information for prenatal genetic counseling.