{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:55:04Z","timestamp":1791482104520,"version":"4.3.4"},"reference-count":74,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI23\/00276"],"award-info":[{"award-number":["PI23\/00276"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FI24\/00139"],"award-info":[{"award-number":["FI24\/00139"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centro de investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras","award":["PIT23"],"award-info":[{"award-number":["PIT23"]}],"id":[{"id":"https:\/\/ror.org\/01ygm5w19","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Outcomes<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0359270","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:24:40Z","timestamp":1791480280000},"page":"e0359270","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["The NBGENS project protocol: Pilot study for genetic newborn screening in Galicia"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6874-2480","authenticated-orcid":true,"given":"Lluis","family":"Lis-L\u00f3pez","sequence":"first","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS)","place":["Santiago de Compostela, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"L\u00f3pez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS)","place":["Santiago de Compostela, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"L\u00f3pez-Valverde","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS)","place":["Santiago de Compostela, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salom\u00e9","family":"Quint\u00e1ns-Lago","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednico Universitario de Santiago de Compostela, CIBERER, MetabERN, RICORS-SAMID","place":["Santiago de Compostela, Spain"],"department":["Department of Forensic Sciences, Pathology, Gynecology and Obstetrics, Pediatrics, Neonatology Service"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno K.","family":"Rodi\u00f1o-Janeiro","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS)","place":["Santiago de Compostela, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. V\u00edctor","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS)","place":["Santiago de Compostela, Spain"]},{"name":"Hospital Cl\u00ednico Universitario de Santiago de Compostela, CIBERER, MetabERN, RICORS-SAMID","place":["Santiago de Compostela, Spain"],"department":["Department of Forensic Sciences, Pathology, Gynecology and Obstetrics, Pediatrics, Neonatology Service"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6895-4140","authenticated-orcid":true,"given":"Francisco","family":"Barros","sequence":"additional","affiliation":[{"name":"CIBERER, Galician Public Foundation of Xenomics Medicine - SERGAS","place":["Santiago de Compostela, Spain"],"department":["Xenomics Medicine Group"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1431-4644","authenticated-orcid":true,"given":"Sof\u00eda","family":"Gouveia","sequence":"additional","affiliation":[{"name":"Utrecht University","place":["Tilburg, the Netherlands"],"department":["Bijvoet Centre for Biomolecular Research"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Serres-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS)","place":["Santiago de Compostela, Spain"]},{"name":"Hospital Cl\u00ednico Universitario de Santiago de Compostela, CIBERER, MetabERN, RICORS-SAMID","place":["Santiago de Compostela, Spain"],"department":["Department of Forensic Sciences, Pathology, Gynecology and Obstetrics, Pediatrics, Neonatology Service"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Garc\u00eda-Villoria","sequence":"additional","affiliation":[{"name":"CDB, Hospital Clinic de Barcelona, IDIBAPS","place":["Barcelona, Spain"],"department":["Division of Inborn Errors of Metabolism-IBC, Department of Biochemistry and Molecular Genetics"]},{"name":"Center for biomedical network research on rare diseases (CIBERER), ISCIII","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda E.","family":"V\u00e1zquez-Mosquera","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS)","place":["Santiago de Compostela, Spain"]},{"name":"Hospital Cl\u00ednico Universitario de Santiago de Compostela, CIBERER, MetabERN, RICORS-SAMID","place":["Santiago de Compostela, Spain"],"department":["Department of Forensic Sciences, Pathology, Gynecology and Obstetrics, Pediatrics, Neonatology Service"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4861-9905","authenticated-orcid":true,"given":"Mar\u00eda Luz","family":"Couce","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS)","place":["Santiago de Compostela, Spain"]},{"name":"Hospital Cl\u00ednico Universitario de Santiago de Compostela, CIBERER, MetabERN, RICORS-SAMID","place":["Santiago de Compostela, Spain"],"department":["Department of Forensic Sciences, Pathology, Gynecology and Obstetrics, Pediatrics, Neonatology Service"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"issue":"4","key":"pone.0359270.ref001","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1093\/jalm\/jfae020","article-title":"Newborn screening: Current practice and our journey over the last 60 years","volume":"9","author":"J Cao","year":"2024","journal-title":"J Appl Lab Med"},{"issue":"2","key":"pone.0359270.ref002","doi-asserted-by":"crossref","DOI":"10.1016\/j.anpedi.2019.05.007","article-title":"Situaci\u00f3n actual del cribado neonatal de enfermedades metab\u00f3licas en Espa\u00f1a y en el mundo","volume":"91","author":"DE Casti\u00f1eras","year":"2019","journal-title":"An Pediatr (Barc)"},{"key":"pone.0359270.ref003","author":"Centers for Disease Control and Prevention","year":"2024"},{"issue":"7","key":"pone.0359270.ref004","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1007\/s00431-022-04470-3","article-title":"Neurological assessment of newborns with spinal muscular atrophy identified through neonatal screening","volume":"181","author":"M Pane","year":"2022","journal-title":"Eur J Pediatr"},{"issue":"4","key":"pone.0359270.ref005","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.ymgme.2011.09.021","article-title":"Evaluation and long-term follow-up of infants with inborn errors of metabolism identified in an expanded screening programme","volume":"104","author":"ML Couce","year":"2011","journal-title":"Mol Genet Metab"},{"key":"pone.0359270.ref006","article-title":"Evaluaci\u00f3n y perspectiva de 20 a\u00f1os de cribado neonatal en Galicia. 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