Abstract
Chromosomal microarray analysis (CMA), recently introduced following conventional cytogenetic technology, can detect submicroscopic copy-number variations (CNVs) in cases previously diagnosed as “cytogenetically benign”. At present, rapid and accurate chromosomal analysis is required in prenatal diagnostics, but prenatal CMA is not widely used due to its high price and long turnaround time. We introduced a new prenatal screening method named digital karyotyping (D-karyo), which utilizes a preimplantation genetic test for the aneuploidy (PGT-A) platform. First, we conducted a preliminary experiment to compare the original PGT-A method to our modified method. Based on the preliminary results, we decided to implement the modified strategy without whole-genome amplification (WGA) and combined it with three analytical software packages. Next, we conducted a prospective study with 824 samples. According to the indication for invasive tests, the D-karyo positive rates were 2.5% and 5.0%, respectively, in the screening positive group with NT ≥ 3.5 mm and the group with fetal abnormalities by ultrasound. D-karyo is a breakthrough modality that can detect submicroscopic CNVs ≥ 1.0 Mb accurately in only 10.5 h for 24 samples at a low cost. Implementing D-karyo as a prenatal rapid screening test will reduce unnecessary CMA and achieve more accurate prenatal genetic testing than G-banding.
Highlights
Conventional cytogenetic karyotyping is performed by G-banding
XHMM w/o whole-genome amplification (WGA) detected 855 kb or larger copy-number variations (CNVs), including terminal deletion and mosaicism that were undetected by XHMM with WGA
The results showed the clear difference between XHMM with WGA and w/o WGA in the terminal deletion case and mosaics
Summary
Conventional cytogenetic karyotyping is performed by G-banding. This analog karyotyping has several disadvantages compared to recent molecular genetic approaches. Numerous reports have been published about the detection rates for pathogenic copy-number variations (CNVs) in fetuses with structural anomalies, detected by ultrasound scanning using CMA, for postnatal diagnosis and prenatal settings [3,4,5,6]. Depending on the type of anomaly groups, the detection rates of pathogenic CNVs are different. The American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) provided the joint recommendation in 2016 that CMA is performed as a prenatal diagnosis for a fetus that has one or more structural anomalies detected by ultrasonography [7]. The UK health service stated that CMA should replace karyotyping from the viewpoint of the detection rate and cost-effectiveness [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
