<b><i>Objective:</i></b> The aim of the study was to assess the diagnostic yield of 2 different next-generation sequencing (NGS) approaches: gene panel and “solo” clinical exome sequencing (solo-CES), in fetuses with structural anomalies and normal chromosomal microarray analysis (CMA), in the absence of a known familial mutation. <b><i>Methodology:</i></b> Gene panels encompassing from 2 to 140 genes, were applied mainly in persistent nuchal fold/fetal hydrops and in large hyperechogenic kidneys. Solo-CES, which entails sequencing the fetus alone and only interpreting the Online Mendelian Inheritance in Man genes, was performed in multisystem or recurrent structural anomalies. <b><i>Results:</i></b> During the study period (2015–2020), 153 NGS studies were performed in 148 structurally abnormal fetuses with a normal CMA. The overall diagnostic yield accounted for 35% (53/153) of samples and 36% (53/148) of the fetuses. Diagnostic yield with the gene panels was 31% (15/49), similar to 37% (38/104) in solo-CES. <b><i>Conclusions:</i></b> A monogenic disease was established as the underlying cause in 35% of selected fetal structural anomalies by gene panels and solo-CES.
Clinical utility of Whole Exome Sequencing for rare Mendelian disorders: phenotypic-driven strategy for a high diagnostic yield and identification of 48 novel variants
