Application of Prenatal Whole Exome Sequencing for Structural Congenital Anomalies-Experience from a Local Prenatal Diagnostic Laboratory

Fetal structural congenital abnormalities (SCAs) complicate 2-3% of all pregnancies. Whole-exome sequencing (WES) has been increasingly adopted prenatally when karyotyping and chromosomal microarray do not yield a diagnosis. This is a retrospective cohort study of 104 fetuses with SCAs identified on antenatal ultrasound in Hong Kong, where whole exome sequencing is performed. Molecular diagnosis was obtained in 25 of the 104 fetuses (24%). The highest diagnostic rate was found in fetuses with multiple SCAs (29.2%), particularly those with involvement of the cardiac and musculoskeletal systems. Variants of uncertain significance were detected in 8 out of the 104 fetuses (7.7%). Our study shows the utility of WES in the prenatal setting, and the extended use of the technology would be recommended in addition to conventional genetic workup.

Automated summary

The study demonstrates the utility of whole-exome sequencing (WES) in prenatal diagnosis of fetal structural congenital abnormalities (SCAs) in Hong Kong. The highest diagnostic rate was found in fetuses with multiple SCAs, particularly involving the cardiac and musculoskeletal systems. The use of WES should be recommended in addition to conventional genetic workup.