All-in-one whole exome sequencing strategy with simultaneous copy number variant, single nucleotide variant and absence-of-heterozygosity analysis in fetuses with structural ultrasound anomalies: A 1-year experience.

Autor: Faas BHW; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Westra D; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., de Munnik SA; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands., van Rij M; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Marcelis C; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Joosten S; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Krapels I; Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands., Vernimmen V; Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands., Heijligers M; Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands., Willemsen MH; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., de Leeuw N; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Rinne T; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Pfundt R; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Smeekens SP; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Stegmann SPA; Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands., Macville M; Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands., Sikkel E; Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands., Coumans A; Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, Maastricht, The Netherlands., Wijnberger L; Department of Obstetrics and Gynaecology, Rijnstate Hospital, Arnhem, The Netherlands., Derks I; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., van Lent-Albrechts J; Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands., Hofste T; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Timmermans R; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., van den End J; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Stevens SJC; Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands., Feenstra I; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Jazyk: angličtina
Zdroj: Prenatal diagnosis [Prenat Diagn] 2023 Apr; Vol. 43 (4), pp. 527-543. Date of Electronic Publication: 2023 Feb 05.
DOI: 10.1002/pd.6314
Abstrakt: 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.
(© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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