Evaluation of the contribution of trio-exome sequencing in selected prenatal indications.

Objective: This study is an example of the contribution of exome sequencing (ES) in selected prenatal indications, while illustrating the complexity of interpreting prenatal genetic testing. Therefore, one of the aims of this study was to better describe antenatal phenotypes. Methods: This was a multicenter, comparative, prospective study assessing high-throughput sequencing performance (targeted gene panel Results: Trio-ES was performed on 86 fetuses, allowed making a definite etiological diagnosis in 28% of cases (24/86). One-third of diagnoses were obtained only after exome analysis (8/24, 33%). The diagnostic yield varied according to the indication and was the highest for vermian hypoplasia (5/12, 42%) and polymalformative syndromes (30%, 8/27) indications. The variants identified were mainly missense variants in ciliopathy (18%, 6/33) and cytoskeleton (15%, 5/33) genes. Among the etiological diagnoses, one fetus carried a postzygotic mosaic variant in Conclusion: In selected indications, the diagnostic yield of ES was close to 30% and varied according to the indications, showing the importance of clearly define the malformations justifying this approach. An etiological diagnosis was made in 23 families, within a timeframe compatible with pregnancy, thus improving the management of the pregnancy and/or the unborn child.