Whole Genome Sequencing in the Evaluation of Fetal Structural Anomalies: A Parallel Test with Chromosomal Microarray Plus Whole Exome Sequencing

Whole genome sequencing (WGS) is a powerful tool for postnatal genetic diagnosis, but relevant clinical studies in the field of prenatal diagnosis are limited. The present study aimed to prospectively evaluate the utility of WGS compared with chromosomal microarray (CMA) and whole exome sequencing (WES) in the prenatal diagnosis of fetal structural anomalies. We performed trio WGS (approximate to 40-fold) in parallel with CMA in 111 fetuses with structural or growth anomalies, and sequentially performed WES when CMA was negative (CMA plus WES). In comparison, WGS not only detected all pathogenic genetic variants in 22 diagnosed cases identified by CMA plus WES, yielding a diagnostic rate of 19.8% (22/110), but also provided additional and clinically significant information, including a case of balanced translocations and a case of intrauterine infection, which might not be detectable by CMA or WES. WGS also required less DNA (100 ng) as input and could provide a rapid turnaround time (TAT, 18 +/- 6 days) compared with that (31 +/- 8 days) of the CMA plus WES. Our results showed that WGS provided more comprehensive and precise genetic information with a rapid TAT and less DNA required than CMA plus WES, which enables it as an alternative prenatal diagnosis test for fetal structural anomalies.

Automated summary

The study aimed to evaluate the utility of whole genome sequencing (WGS) compared with chromosomal microarray (CMA) and whole exome sequencing (WES) in prenatal diagnosis of fetal structural anomalies. Results showed that WGS provided more comprehensive and precise genetic information with a faster turnaround time and less DNA required than CMA plus WES, making it a potential alternative for prenatal diagnosis of fetal structural anomalies.