| Objective To explore the application of low-depth copy number variation sequencing (CNV-Seq) combined with karyotyping in the diagnosis of fetal chromosomal mosaicism. Methods The pregnant women who underwent the routine prenatal diagnosis at the Prenatal Diagnostic Center, the First Affiliated Hospital of University of Science and Technology of China were selected as subjects, and 3320 amniotic fluid samples were obtained from ultrasound-guided amniocentesis. All the extracted samples from 3320 cases undergone amniocentesis were subjected to chromosomal karyotyping (two-line independent operation) and CNV-Seq detection, respectively. Then, the cases diagnosed as fetal mosaicism were collected for further retrospective analyses. Results Among the 3320 amniotic fluids samples, 19 mosaicism cases were detected (positive rate was 0.57%), of which 16 cases were detected by chromosomal karyotyping (positive rate was 0.48%), while 12 cases were detected by CNV-Seq (positive rate was 0.36%). Specifically, eight mosaicism cases were detected from pregnant women with abnormal non-invasive prenatal test (NIPT) results, five mosaicism cases were detected from pregnant women with abnormal ultrasound or nuchal translucency (NT) thickness, two mosaicism cases were detected from pregnant women with advanced age, four mosaicism cases were detected from pregnant women with high-risk Down's syndrome screening. Among all the 19 mosaicism cases, nine were autosomal mosaicisms, while the other ten cases were sex chromosomal abnormalities. Notably, three cases without mosaicisms diagnosed by karyotyping, were detected as mosaicisms by CNV-Seq, which were further verified to be true mosaicisms by FISH analyses. Conclusion CNV-Seq technology combined with karyotyping could avoid the misdiagnosis of fetal chromosomal mosaicism with single technology, which may provide more convincing laboratory results for prenatal genetic counseling. |
