| Affiliation: | 1. Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands;2. Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands;3. Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands;4. Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands;5. Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, Maastricht, The Netherlands;6. Department of Obstetrics and Gynaecology, Rijnstate Hospital, Arnhem, The Netherlands |
| Abstract: | Objective We performed a 1-year evaluation of a novel strategy of simultaneously analyzing single nucleotide variants (SNVs), copy number variants (CNVs) and copy-number-neutral Absence-of-Heterozygosity from Whole Exome Sequencing (WES) data for prenatal diagnosis of fetuses with ultrasound (US) anomalies and a non-causative QF-PCR result. Methods After invasive diagnostics, whole exome parent-offspring trio-sequencing with exome-wide CNV analysis was performed in pregnancies with fetal US anomalies and a non-causative QF-PCR result (WES-CNV). On request, additional SNV-analysis, restricted to (the) requested gene panel(s) only (with the option of whole exome SNV-analysis afterward) was performed simultaneously (WES-CNV/SNV) or as rapid SNV-re-analysis, following a normal CNV analysis. Results In total, 415 prenatal samples were included. 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 2 weeks after sampling. For SNV-re-analysis during pregnancy, turn-around-times (TATs) varied between one and 8 days. Conclusion We show 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. |
