[A case of mosaicism involving trisomy 21, maternal uniparental isodisomy, and normal diploid cells: Challenges and reflections in prenatal diagnosis].

Objective: To report on a case of mosaicism involving trisomy 21, maternal uniparental isodisomy, and normal diploid cells in uncultured amniocytes, and to explore the discrepancies between conventional cytogenetic and molecular cytogenetic techniques during prenatal diagnosis.

Methods: A 30-year-old pregnant woman who presented to Boai Hospital of Zhongshan on June 27, 2023 has undergone amniocentesis at 16 weeks of gestation. The amniotic fluid sample was subjected to quantitative fluorescent PCR (QF-PCR), G-banded karyotype analysis, and chromosomal microarray analysis (CMA). The discrepancies between the results of each method were analyzed. This study was approved by Medical Ethics Committee of Boai Hospital of Zhongshan (Ethics No.: KY-2024-001-01).

Results: Non-invasive prenatal testing (NIPT) at 12 weeks indicated a high risk of trisomy 21. QF-PCR of uncultured amniocytes revealed a pattern of trisomy 21. After one week of cell culture, G-banding analysis showed mos 47,XX,+21[1]/46,XX[72]. CMA revealed a homozygous state of chromosome 21 in cultured cells, while uncultured amniocytes showed mosaic trisomy 21 with an estimated proportion of 50%. These findings suggested a complex chromosomal mosaicism in the fetus, which may result from a trisomy rescue event during early embryogenesis, leading to coexistence of three cell lines including trisomy 21, maternal uniparental isodisomy, and normal diploid cells.

Conclusion: In prenatal diagnosis, discrepancies may arise between QF-PCR and conventional chromosomal karyotyping analysis, particularly in complex genetic phenomena such as trisomy rescue and uniparental disomy. For cases where NIPT indicated a high risk of trisomy 21 but G-banding karyotype analysis yielded a normal result, further molecular genetic testing using uncultured cells is recommended.