Analytical Validation of a Genomic Newborn Screening Workflow.

[en] Newborn screening (NBS) has evolved significantly since its inception, yet many treatable rare diseases remain unscreened due to technical limitations. The BabyDetect study used gene panel sequencing to expand NBS to treatable conditions not covered by conventional biochemical screening. We present here the analytical validation of this workflow, assessing sensitivity, precision, and reproducibility using dried blood spots from newborns. We implemented strict quality control thresholds for sequencing, coverage, and contamination, ensuring high reliability. Longitudinal monitoring confirmed consistent performance across more than 5900 samples. Automation of DNA extraction improved scalability, and a panel redesign enhanced the coverage and selection of targeted regions. By focusing on known pathogenic/likely pathogenic variants, we minimized false positives and maintained clinical actionability. Our findings demonstrate that gene panel sequencing-based NBS is feasible, accurate, and scalable, addressing critical gaps in current screening programs.

Disciplines :

Pediatrics

Author, co-author :

Hovhannesyan, Kristine ; Centre Hospitalier Universitaire de Liège - CHU > > Service de neurologie (CHR)

Helou, Laura ; Université de Liège - ULiège > Département des sciences cliniques

Charloteaux, Benoit ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique

JACQUEMIN, VALERIE ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pédiatrie

Piazzon, Flavia; Division of Child Neurology, Department of Pediatrics, Reference Center for Neuromuscular Diseases, CHU of Liege, University of Liege, Bd du Douzième de Ligne 1, 4000 Liege, Belgium

Mni, Myriam ; Université de Liège - ULiège > GIGA > GIGA Molecular & Computational Biology - Unit of Animal Genomics

Flohimont, Charlotte ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pédiatrie

Fasquelle, Corinne ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique

Mashhadizadeh, Davood ; Division of Child Neurology, Department of Pediatrics, Reference Center for Neuromuscular Diseases, CHU of Liege, University of Liege, Bd du Douzième de Ligne 1, 4000 Liege, Belgium

Dangouloff, Tamara ; Université de Liège - ULiège > Département des sciences cliniques

More authors (4 more)

Language :

English

Title :

Analytical Validation of a Genomic Newborn Screening Workflow.

Publication date :

13 November 2025

Journal title :

International Journal of Neonatal Screening

eISSN :

2409-515X

Publisher :

MDPI AG, Switzerland

Volume :

Issue :

Pages :

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://www.mdpi.com/2409-515X/11/4/91/pdf

Funders :

Sanofi
Orchard Therapeutics
Takeda
Leon Fredericq Foundation
Région Wallonne

Available on ORBi :

since 28 December 2025

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