The NBGENS project protocol: Pilot study for genetic newborn screening in Galicia
6 affiliations
- 1Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
- 2Department of Forensic Sciences, Pathology, Gynecology and Obstetrics, Pediatrics, Neonatology Service, Hospital Clínico Universitario de Santiago de Compostela, CIBERER, MetabERN, RICORS-SAMID, Santiago de Compostela, Spain
- 3Xenomics Medicine Group, CIBERER, Galician Public Foundation of Xenomics Medicine - SERGAS, Santiago de Compostela, Spain
- 4Bijvoet Centre for Biomolecular Research, Utrecht University, Tilburg, the Netherlands
- 5Division of Inborn Errors of Metabolism-IBC, Department of Biochemistry and Molecular Genetics, CDB, Hospital Clinic de Barcelona, IDIBAPS, Barcelona, Spain
- 6Center for biomedical network research on rare diseases (CIBERER), ISCIII, Madrid, Spain
Abstract
Background: Conventional newborn screening (NBS) relies on mainly biochemical assays and remains limited by its dependence on detectable biomarkers within a narrow postnatal window, leaving many treatable genetic disorders unidentified. Advances in next-generation sequencing have enabled projects of genomic newborn screening, which may expand the spectrum of detectable conditions. However, challenges persist regarding variant interpretation, reporting criteria, and integration into public healthcare systems. Methods: NBGenS is a prospective, single-center pilot study in Spain that will evaluate the feasibility of integrating whole exome sequencing (WES) into routine NBS. The study will recruit 550 newborns at the University Clinical Hospital of Santiago de Compostela. DNA will be extracted from residual dried blood spots (DBS) obtained through NBS. WES and clinical interpretation will be restricted to a virtual panel of genes associated with severe, highly-penetrant, pediatric-onset diseases for which early intervention is available. Variant interpretation will follow ACMG/AMP and ClinGen recommendations, and only pathogenic or likely pathogenic variants will be considered reportable. Untargeted metabolomics using DBS will be applied in selected cases, particularly for prioritised variants of uncertain significance (VUS), to provide complementary biochemical evidence that may contribute to variant classification. Clinical follow-up, psychosocial assessment, pharmacogenetic analysis, and health economic evaluation will also be incorporated into the study design. Outcomes: The project will establish and evaluate a comprehensive clinical workflow encompassing recruitment, sequencing, interpretation, reporting, and follow-up. Key outcomes will include diagnostic yield, parental acceptance, psychological impact, cost-effectiveness, clinical utility, and the added value of metabolomic integration for resolving VUS. Conclusion: NBGenS represents one of the first prospective public healthcare pilot studies integrating genomic sequencing and untargeted metabolomics within an established NBS program. The study will generate empirical evidence on the clinical, ethical, psychosocial, and economic implications of neonatal genomic screening and may inform future policy decisions regarding its implementation within national health systems.
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BibTeX
@article{lislopez2026nbgens,
title = {{The NBGENS project protocol: Pilot study for genetic newborn screening in Galicia}},
author = {Lluis Lis-López and Catalina López-López and Laura López-Valverde and Salomé Quintáns-Lago and Bruno K. Rodiño-Janeiro and J. Víctor Álvarez and Francisco Barros and Sofía Gouveia and Mariana Serres-Gómez and Judit García-Villoria and María E. Vázquez-Mosquera and María Luz Couce},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0359270},
url = {https://doi.org/10.1371/journal.pone.0359270},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The NBGENS project protocol: Pilot study for genetic newborn screening in Galicia
AU - Lluis Lis-López
AU - Catalina López-López
AU - Laura López-Valverde
AU - Salomé Quintáns-Lago
AU - Bruno K. Rodiño-Janeiro
AU - J. Víctor Álvarez
AU - Francisco Barros
AU - Sofía Gouveia
AU - Mariana Serres-Gómez
AU - Judit García-Villoria
AU - María E. Vázquez-Mosquera
AU - María Luz Couce
PY - 2026
DA - 2026/10/08
JO - PLOS One
DO - 10.1371/journal.pone.0359270
UR - https://doi.org/10.1371/journal.pone.0359270
AB - Background: Conventional newborn screening (NBS) relies on mainly biochemical assays and remains limited by its dependence on detectable biomarkers within a narrow postnatal window, leaving many treatable genetic disorders unidentified. Advances in next-generation sequencing have enabled projects of genomic newborn screening, which may expand the spectrum of detectable conditions. However, challenges persist regarding variant interpretation, reporting criteria, and integration into public healthcare systems. Methods: NBGenS is a prospective, single-center pilot study in Spain that will evaluate the feasibility of integrating whole exome sequencing (WES) into routine NBS. The study will recruit 550 newborns at the University Clinical Hospital of Santiago de Compostela. DNA will be extracted from residual dried blood spots (DBS) obtained through NBS. WES and clinical interpretation will be restricted to a virtual panel of genes associated with severe, highly-penetrant, pediatric-onset diseases for which early intervention is available. Variant interpretation will follow ACMG/AMP and ClinGen recommendations, and only pathogenic or likely pathogenic variants will be considered reportable. Untargeted metabolomics using DBS will be applied in selected cases, particularly for prioritised variants of uncertain significance (VUS), to provide complementary biochemical evidence that may contribute to variant classification. Clinical follow-up, psychosocial assessment, pharmacogenetic analysis, and health economic evaluation will also be incorporated into the study design. Outcomes: The project will establish and evaluate a comprehensive clinical workflow encompassing recruitment, sequencing, interpretation, reporting, and follow-up. Key outcomes will include diagnostic yield, parental acceptance, psychological impact, cost-effectiveness, clinical utility, and the added value of metabolomic integration for resolving VUS. Conclusion: NBGenS represents one of the first prospective public healthcare pilot studies integrating genomic sequencing and untargeted metabolomics within an established NBS program. The study will generate empirical evidence on the clinical, ethical, psychosocial, and economic implications of neonatal genomic screening and may inform future policy decisions regarding its implementation within national health systems.
SN - 1932-6203
ER -