{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T02:54:54Z","timestamp":1786589694320,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJNS"],"abstract":"<jats:p>As biotechnologies advance and better treatment regimens emerge, there is a trend toward applying more advanced technologies and adding more conditions to the newborn screening (NBS) panel. In the current Recommended Uniform Screening Panel (RUSP), all conditions but one, congenital hypothyroidism, have well-defined genes and inheritance patterns, so it is beneficial to incorporate molecular testing in NBS when it is necessary and appropriate. Indeed, the applications of molecular technologies have taken NBS to previously uncharted territory. In this paper, based on our own program experience and what has been reported in the literature, we describe current practices regarding the applications of molecular technologies in routine NBS practice in the era of genomic and precision medicine.<\/jats:p>","DOI":"10.3390\/ijns6040080","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T09:02:03Z","timestamp":1602752523000},"page":"80","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Translating Molecular Technologies into Routine Newborn Screening Practice"],"prefix":"10.3390","volume":"6","author":[{"given":"Sarah M.","family":"Furnier","sequence":"first","affiliation":[{"name":"Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"},{"name":"Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen S.","family":"Durkin","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"},{"name":"Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA"},{"name":"Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8707-1834","authenticated-orcid":false,"given":"Mei W.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"},{"name":"Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA"},{"name":"Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"},{"name":"Wisconsin State Laboratory of Hygiene, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"key":"ref_1","unstructured":"Centers for Disease Control and Prevention (2012). CDC grand rounds: Newborn screening and improved outcomes. MMWR Morbid. Mortal. Wkly. Rep., 61, 390\u2013393."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/BF00283692","article-title":"Molecular genetic diagnosis of sickle cell disease using dried blood specimens on blotters used for newborn screening","volume":"81","author":"Jinks","year":"1989","journal-title":"Hum. Genet."},{"key":"ref_3","first-page":"616","article-title":"Application of DNA analysis in a population-screening program for neonatal diagnosis of cystic fibrosis (CF): Comparison of screening protocols","volume":"52","author":"Gregg","year":"1993","journal-title":"Am. J. Hum. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.jcf.2011.02.001","article-title":"Optimal DNA tier for the IRT\/DNA algorithm determined by CFTR mutation results over 14 years of newborn screening","volume":"10","author":"Baker","year":"2011","journal-title":"J. Cyst. Fibros."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1136\/bmj.302.6787.1237","article-title":"Neonatal screening strategy for cystic fibrosis using immunoreactive trypsinogen and direct gene analysis","volume":"302","author":"Ranieri","year":"1991","journal-title":"Brit. Med. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jcf.2006.05.008","article-title":"A survey of newborn screening for cystic fibrosis in Europe","volume":"6","author":"Southern","year":"2007","journal-title":"J. Cyst. Fibros."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.jaci.2007.08.043","article-title":"Population-based newborn screening for severe combined immunodeficiency: Steps toward implementation","volume":"120","author":"Puck","year":"2007","journal-title":"J. Allergy Clin. Immun."},{"key":"ref_8","first-page":"1","article-title":"Applying public health strategies to primary immunodeficiency diseases: A potential approach to genetic disorders","volume":"53","author":"Lindegren","year":"2004","journal-title":"MMWR Recomm. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.jaci.2004.10.012","article-title":"Development of population-based newborn screening for severe combined immunodeficiency","volume":"115","author":"Chan","year":"2005","journal-title":"J. Allergy Clin. Immun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/25374","article-title":"Changes in thymic function with age and during the treatment of HIV infection","volume":"396","author":"Douek","year":"1998","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.jaci.2009.04.007","article-title":"Development of a routine newborn screening protocol for severe combined immunodeficiency","volume":"124","author":"Baker","year":"2009","journal-title":"J. Allergy Clin. Immun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s10875-011-9609-4","article-title":"Newborn screening for severe combined immunodeficiency; The Wisconsin experience (2008\u20132011)","volume":"32","author":"Verbsky","year":"2012","journal-title":"J. Clin. Immunol."},{"key":"ref_13","unstructured":"(2020, September 21). Newborn Screening for Severe Combined Immunodeficiency a Summary of the Evidence and Advisory Committee Decision, Available online: https:\/\/www.hrsa.gov\/sites\/default\/files\/hrsa\/advisory-committees\/heritable-disorders\/rusp\/previous-nominations\/scid-27-june-2018.pdf."},{"key":"ref_14","unstructured":"NewSTEPs (2020, September 21). Newborn Screening Status for All Disorder. Available online: https:\/\/www.newsteps.org\/resources\/data-visualizations\/newborn-screening-status-all-disorders."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1001\/jama.2014.9132","article-title":"Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States","volume":"312","author":"Kwan","year":"2014","journal-title":"JAMA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"782","DOI":"10.3389\/fimmu.2018.00782","article-title":"High incidence of severe combined immunodeficiency disease in Saudi Arabia detected through combined T cell receptor excision circle and next generation sequencing of newborn dried blood spots","volume":"9","author":"Jabr","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.3389\/fimmu.2019.02406","article-title":"First universal newborn screening program for severe combined immunodeficiency in Europe. Two-years\u2019 experience in Catalonia (Spain)","volume":"10","author":"Colobran","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1007\/s10875-018-0550-7","article-title":"Newborn screening for severe combined immunodeficiency: Analytic and clinical performance of the T cell receptor excision circle assay in France (DEPISTREC study)","volume":"38","author":"Audrain","year":"2018","journal-title":"J. Clin. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s10875-016-0347-5","article-title":"Newborn screening for severe primary immunodeficiency diseases in Sweden\u2014A 2-year pilot TREC and KREC screening study","volume":"37","author":"Barbaro","year":"2017","journal-title":"J. Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Blom, M., Bredius, R.G., Weijman, G., Dekkers, E.H., Kemper, E.A., den Akker-van Marle, V., Elske, M., Van der Ploeg, C.P., Van der Burg, M., and Schielen, P.C. (2018). Introducing newborn screening for severe combined immunodeficiency (SCID) in the Dutch neonatal screening program. Int. J. Neonatal Screen., 4.","DOI":"10.3390\/ijns4040040"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Chien, Y.-H., Yu, H.-H., Lee, N.-C., Ho, H.-C., Kao, S.-M., Lu, M.-Y., Jaing, T.-H., Lee, W.-I., Chang, K.-W., and Shieh, C.-C. (2017). Newborn screening for severe combined immunodeficiency in Taiwan. Int. J. Neonatal Screen., 3.","DOI":"10.3390\/ijns3030016"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1590\/1984-0462\/;2017;35;1;00013","article-title":"Newborn screening for severe combined immunodeficiencies using TRECs and KRECs: Second pilot study in Brazil","volume":"35","author":"Kanegae","year":"2017","journal-title":"Rev. Paul. Pediatr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3717","DOI":"10.1182\/blood-2018-99-118261","article-title":"Combination of TREC measurement and next-generation sequencing in newborn screening for severe combined immunodeficiency: A pilot program in Japan","volume":"132","author":"Muramatsu","year":"2018","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Rechavi, E., Lev, A., Saraf-Levy, T., Etzioni, A., Almashanu, S., and Somech, R. (2017). Newborn screening for severe combined immunodeficiency in Israel. Int. J. Neonatal Screen., 3.","DOI":"10.3390\/ijns3020013"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s001090100271","article-title":"T cell receptor excision circles as markers for recent thymic emigrants: Basic aspects, technical approach, and guidelines for interpretation","volume":"79","author":"Hazenberg","year":"2001","journal-title":"J. Mol. Med."},{"key":"ref_26","unstructured":"Association of Public Health Laboratories, and NewSTEPs (2020, September 21). Expanding the Reach of SCID Testing: A Report on the Severe Combined Immunodeficiency Newborn Screening Implementation Experience. Available online: https:\/\/www.aphl.org\/aboutAPHL\/publications\/Documents\/NBS-2018Nov-SCID-Implementation-Report.pdf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.3389\/fimmu.2020.01417","article-title":"Second-tier next generation sequencing integrated in nationwide newborn screening provides rapid molecular diagnostics of severe combined immunodeficiency","volume":"11","author":"Strand","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.ncl.2015.07.004","article-title":"Spinal muscular atrophy","volume":"33","author":"Kolb","year":"2015","journal-title":"Neurol. Clin."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.nmd.2018.01.003","article-title":"Correlation between SMA type and SMN2 copy number revisited: An analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases","volume":"28","author":"Calucho","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"ref_30","first-page":"518","article-title":"Natural history in proximal spinal muscular atrophy: Clinical analysis of 445 patients and suggestions for a modification of existing classifications","volume":"52","author":"Zerres","year":"1995","journal-title":"Ann. Neurol."},{"key":"ref_31","unstructured":"(2020, September 21). Newborn Screening for Spinal Muscular Atrophy a Summary of the Evidence and Advisory Committee Decision, Available online: https:\/\/www.hrsa.gov\/sites\/default\/files\/hrsa\/advisory-committees\/heritable-disorders\/rusp\/previous-nominations\/sma-consumer-summary.pdf."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.nmd.2019.02.003","article-title":"Newborn screening for SMA in southern Belgium","volume":"29","author":"Boemer","year":"2019","journal-title":"Neuromuscul. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.jpeds.2017.06.042","article-title":"Presymptomatic diagnosis of spinal muscular atrophy through newborn screening","volume":"190","author":"Chien","year":"2017","journal-title":"J. Pediatr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41436-019-0673-0","article-title":"The implementation of newborn screening for spinal muscular atrophy: The Australian experience","volume":"22","author":"Kariyawasam","year":"2020","journal-title":"Genet. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1038\/s41436-020-0824-3","article-title":"Implementation of population-based newborn screening reveals low incidence of spinal muscular atrophy","volume":"22","author":"Kay","year":"2020","journal-title":"Genet. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3233\/JND-190428","article-title":"One year of newborn screening for SMA\u2013Results of a German pilot project","volume":"6","author":"Vill","year":"2019","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1542\/peds.113.6.1573","article-title":"Population-based newborn screening for genetic disorders when multiple mutation DNA testing is incorporated: A cystic fibrosis newborn screening model demonstrating increased sensitivity but more carrier detections","volume":"113","author":"Comeau","year":"2004","journal-title":"Pediatrics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s10545-007-0584-0","article-title":"Newborn screening for cystic fibrosis: Techniques and strategies","volume":"30","author":"Wilcken","year":"2007","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/gim.2014.209","article-title":"Improving newborn screening for cystic fibrosis using next-generation sequencing technology: A technical feasibility study","volume":"18","author":"Baker","year":"2016","journal-title":"Genet. Med."},{"key":"ref_40","unstructured":"United States Cystic Fibrosis Foundation, John Hopkins University, and The Hospital for Sick Kids (2020, September 21). CFTR2: Clinical and Functional Translation of CFTR. Available online: https:\/\/cftr2.org\/."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.jcf.2015.01.001","article-title":"Cystic fibrosis screen positive, inconclusive diagnosis (CFSPID): A new designation and management recommendations for infants with an inconclusive diagnosis following newborn screening","volume":"14","author":"Munck","year":"2015","journal-title":"J. Cyst. Fibros."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/gim.2017.32","article-title":"Genomic sequencing in cystic fibrosis newborn screening: What works best, two-tier predefined CFTR mutation panels or second-tier CFTR panel followed by third-tier sequencing?","volume":"19","author":"Currier","year":"2017","journal-title":"Genet. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1002\/ppul.24564","article-title":"Cystic fibrosis newborn screening in Denmark: Experience from the first 2 years","volume":"55","author":"Skov","year":"2020","journal-title":"Pediatr. Pulm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e88","DOI":"10.1093\/nar\/29.17.e88","article-title":"An efficient procedure for genotyping single nucleotide polymorphisms","volume":"29","author":"Ye","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e20182516","DOI":"10.1542\/peds.2018-2516","article-title":"Developmental outcomes in Duarte galactosemia","volume":"143","author":"Carlock","year":"2019","journal-title":"Pediatrics"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ymgme.2014.07.009","article-title":"Inborn errors of metabolism identified via newborn screening: Ten-year incidence data and costs of nutritional interventions for research agenda planning","volume":"113","author":"Therrell","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ymgme.2020.01.006","article-title":"Branched-chain \u03b1-ketoacid dehydrogenase deficiency (maple syrup urine disease): Treatment, biomarkers, and outcomes","volume":"129","author":"Strauss","year":"2020","journal-title":"Mol. Genet. Metab."},{"key":"ref_48","unstructured":"Erasmus University Medical Center (2020, September 21). Pompe Disease GAA Variant Database. Available online: http:\/\/cluster15.erasmusmc.nl\/klgn\/pompe\/mutations.html?lang=en."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1002\/humu.23878","article-title":"GAA variants and phenotypes among 1079 patients with Pompe disease: Data from the Pompe Registry","volume":"40","author":"Reuser","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1111\/jpc.14428","article-title":"Integration of congenital cytomegalovirus screening within a newborn hearing screening programme","volume":"55","author":"Beswick","year":"2019","journal-title":"J. Paediatr Child. H."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1001\/jamapediatrics.2016.2016","article-title":"Cost-effectiveness of universal and targeted newborn screening for congenital cytomegalovirus infection","volume":"170","author":"Gantt","year":"2016","journal-title":"JAMA Pediatr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1001\/jamaneurol.2019.1206","article-title":"Maximizing the benefit of life-saving treatments for Pompe disease, spinal muscular atrophy, and Duchenne muscular dystrophy through newborn screening: Essential steps","volume":"76","author":"Baker","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/ana.24316","article-title":"Cystic fibrosis newborn screening: A model for neuromuscular disease screening?","volume":"77","author":"Scully","year":"2015","journal-title":"Ann. Neurol."}],"updated-by":[{"DOI":"10.3390\/ijns7040066","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000}}],"container-title":["International Journal of Neonatal Screening"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2409-515X\/6\/4\/80\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T14:26:08Z","timestamp":1754231168000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2409-515X\/6\/4\/80"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,15]]},"references-count":53,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijns6040080"],"URL":"https:\/\/doi.org\/10.3390\/ijns6040080","relation":{"correction":[{"id-type":"doi","id":"10.3390\/ijns7040066","asserted-by":"object"}]},"ISSN":["2409-515X"],"issn-type":[{"value":"2409-515X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,15]]}}}