Exploring the application of copy number variation sequencing in
prenatal diagnosis
Abstract
Objective: To explore whether CNV-seq can be used as a first-tier
diagnostic method or even replace karyotyping for prenatal diagnosis
alone. Method: A retrospective study was conducted to 4230 amniocentesis
samples with CNV-seq detection and G-banding karyotyping simultaneously.
The indications for prenatal diagnosis included abnormal result on
Down’s Syndrome Screening, abnormal fetal ultrasound, abnormal result on
noninvasive prenatal screening, and so on. The results that lead to
birth defects definitely were defined as abnormalities, which included
aneuploidy, mosaic aneuploidy, large deletion/duplication and pathogenic
copy number variations (pCNVs). Results: 278 cases of abnormalities was
identified by karyotyping with an abnormal detection rate of
6.69%(283/4230). In addition, for all the abnormalities identified by
karyotyping, CNV-seq also identified another 58 cases of abnormalities.
A total of 341 cases of abnormalities were identified by CNV-seq with an
abnormal detection rate of 8.06%(341/4230), higher than that of
karyotyping. Abnormal detection rate of CNV-seq for the groups with
abnormal result on noninvasive prenatal screening, abnormal fetal
ultrasound, abnormal parental chromosome, adverse pregnancy history,
abnormal result on Down’s Syndrome Screening, volunory testing and
advanced maternal age were increased by 2.53%, 1.91%, 1.44%, 1.24%,
1.01%, 0.99% and 0.62% over the karyotyping respectively. Conclusion:
CNV-seq and karyotyping had the same effectiveness in identifying
aneuploidies, but CNV-seq had absolute superiority in the detection of
low proportion of mosaics, imbalanced structural abnormalities. This
prevents the birth of fetuses with these chromosome abnormalities that
cannot be identified by karyotyping. CNV-seq can replace karyotyping in
prenatal diagnosis for chromosome test alone.