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.


Journal

Prenatal diagnosis
ISSN: 1097-0223
Titre abrégé: Prenat Diagn
Pays: England
ID NLM: 8106540

Informations de publication

Date de publication:
04 2023
Historique:
revised: 06 01 2023
received: 07 10 2022
accepted: 11 01 2023
medline: 18 4 2023
pubmed: 18 1 2023
entrez: 17 1 2023
Statut: ppublish

Résumé

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. 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. 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. 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.

Identifiants

pubmed: 36647814
doi: 10.1002/pd.6314
doi:

Substances chimiques

Nucleotides 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

527-543

Informations de copyright

© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.

Références

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Auteurs

Brigitte H W Faas (BHW)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Dineke Westra (D)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Sonja A 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.

Maartje van Rij (M)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Carlo Marcelis (C)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Sara Joosten (S)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Ingrid Krapels (I)

Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.

Vivian Vernimmen (V)

Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.

Malou Heijligers (M)

Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.

Marjolein H Willemsen (MH)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Nicole de Leeuw (N)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Tuula Rinne (T)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Rolph Pfundt (R)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Sanne P Smeekens (SP)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Sander P A Stegmann (SPA)

Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.

Merryn Macville (M)

Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.

Esther Sikkel (E)

Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands.

Audrey Coumans (A)

Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, Maastricht, The Netherlands.

Lia Wijnberger (L)

Department of Obstetrics and Gynaecology, Rijnstate Hospital, Arnhem, The Netherlands.

Irma Derks (I)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Josefa van Lent-Albrechts (J)

Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.

Tom Hofste (T)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Raoul Timmermans (R)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Janneke van den End (J)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Servi J C Stevens (SJC)

Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands.

Ilse Feenstra (I)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

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