All‐in‐one whole exome sequencing strategy with simultaneous CNV‐, SNV‐ and Absence‐of‐Heterozygosity analysis in fetuses with structural ultrasound anomalies: A one year’s experience.

The authors performed a one‐year evaluation of a novel strategy of simultaneously analyzing SNVs, CNVs and copy‐number‐neutral Absence‐of Heterozygosity from Whole Exome Sequencing (WES) data for prenatal diagnosis of fetuses with ultrasound anomalies and a non‐causative QF‐PCR result. Following a non‐causative QF‐PCR result, WES‐CNV analysis was initially requested for 74.3% of the chorionic villus (CV) samples and 45% of the amniotic fluid (AF) samples. In case WES‐CNV analysis did not reveal a causative aberration, SNV‐re‐analysis was requested in 41.7% of the CV samples and 17.5% of the AF samples. All initial analyses could be finished within two weeks after sampling. For SNV‐re‐analysis during pregnancy, turn‐around‐times (TATs) varied between one and eight days. The study demonstrated a highly efficient all‐in‐one WES‐based strategy, with short TATs and the option of rapid SNV‐re‐analysis after a normal CNV result.