{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:23:36Z","timestamp":1791912216775,"version":"4.3.4"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sanofi","award":["SGZ-2019-12843"],"award-info":[{"award-number":["SGZ-2019-12843"]}]},{"DOI":"10.13039\/501100024091","name":"Orchard Therapeutics","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100024091","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Takeda"},{"name":"L\u00e9on Fr\u00e9d\u00e9ricq Foundation"},{"name":"LaCAR MDx"},{"DOI":"10.13039\/100018985","name":"R\u00e9gion Wallonne","doi-asserted-by":"crossref","award":["1710180"],"award-info":[{"award-number":["1710180"]}],"id":[{"id":"10.13039\/100018985","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJNS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijns11040091","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:50:16Z","timestamp":1760107816000},"page":"91","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Analytical Validation of a Genomic Newborn Screening Workflow"],"prefix":"10.3390","volume":"11","author":[{"given":"Kristine","family":"Hovhannesyan","sequence":"first","affiliation":[{"name":"Biochemical Genetics Laboratory, CHU of Liege, University of Liege, Avenue de l\u2019H\u00f4pital 1, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0608-5861","authenticated-orcid":false,"given":"Laura","family":"Helou","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, CHU of Liege, University of Liege, Avenue de l\u2019H\u00f4pital 1, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4282-9688","authenticated-orcid":false,"given":"Benoit","family":"Charloteaux","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, CHU of Liege, University of Liege, Avenue de l\u2019H\u00f4pital 1, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Jacquemin","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, CHU of Liege, University of Liege, Avenue de l\u2019H\u00f4pital 1, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Piazzon","sequence":"additional","affiliation":[{"name":"Division of Child Neurology, Department of Pediatrics, Reference Center for Neuromuscular Diseases, CHU of Liege, University of Liege, Bd du Douzi\u00e8me de Ligne 1, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Mni","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, CHU of Liege, University of Liege, Avenue de l\u2019H\u00f4pital 1, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Flohimont","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, CHU of Liege, University of Liege, Avenue de l\u2019H\u00f4pital 1, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Fasquelle","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, CHU of Liege, University of Liege, Avenue de l\u2019H\u00f4pital 1, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4621-0173","authenticated-orcid":false,"given":"Davood","family":"Mashhadizadeh","sequence":"additional","affiliation":[{"name":"Division of Child Neurology, Department of Pediatrics, Reference Center for Neuromuscular Diseases, CHU of Liege, University of Liege, Bd du Douzi\u00e8me de Ligne 1, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5435-4774","authenticated-orcid":false,"given":"Tamara","family":"Dangouloff","sequence":"additional","affiliation":[{"name":"Division of Child Neurology, Department of Pediatrics, Reference Center for Neuromuscular Diseases, CHU of Liege, University of Liege, Bd du Douzi\u00e8me de Ligne 1, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Bours","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, CHU of Liege, University of Liege, Avenue de l\u2019H\u00f4pital 1, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9270-4061","authenticated-orcid":false,"given":"Laurent","family":"Servais","sequence":"additional","affiliation":[{"name":"MDUK Oxford Neuromuscular Centre, NIHR Oxford Biomedical Research Centre, University of Oxford, John Radcliffe, Headington, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8750-6692","authenticated-orcid":false,"given":"Leonor","family":"Palmeira","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, CHU of Liege, University of Liege, Avenue de l\u2019H\u00f4pital 1, 4000 Liege, 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