{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:56:39Z","timestamp":1791820599065,"version":"4.3.4"},"reference-count":19,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T00:00:00Z","timestamp":1725840000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Newborn screening (NBS) for primary carnitine deficiency (PCD) has poor performance. This study aimed to evaluate the feasibility of incorporating next\u2010generation sequencing (NGS) as a second\u2010tier PCD test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Between March and December 2020, 60,070 newborns were screened for inherited metabolic disorders. Newborns with free carnitine (C0) levels below 8.5\u2009\u03bcmol\/L were selected for second\u2010tier genetic testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 130 (0.22%) newborns with low C0 levels underwent second\u2010tier genetic testing, 87 (66.92%) had positive genetic testing results, and 30 (23.08%) carried pathogenic variants of the <jats:italic>SLC22A5<\/jats:italic> gene. Six newborns were diagnosed with PCD. The incidence of PCD was approximately 1 in 1:10,012 newborns. The PPV reached 20% after combining with second\u2010tier NGS. Of the eight variants identified in patients with PCD, the three most common variants were c.760C&gt;T (p.Arg254*), c.51C&gt;G (p.Phe17Leu), and c.1400C&gt;G (p.Ser467Cys). The C0 levels of patients with PCD were significantly lower than those of PCD carriers (<jats:italic>p<\/jats:italic>\u2009=\u20090.0026) and PCD\u2010negative individuals (<jats:italic>p<\/jats:italic>\u2009=\u20090.0005).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results showed that the PPV reached 20% after combining with second\u2010tier NGS. The MS\/MS\u2010based NBS and second\u2010tier NGS combination can effectively reduce the false\u2010positive rate and detect PCD in patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70003","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T13:29:30Z","timestamp":1725888570000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Incorporating Next\u2010Generation Sequencing as a Second\u2010Tier Test for Primary Carnitine Deficiency"],"prefix":"10.1002","volume":"12","author":[{"given":"Yiming","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Quanzhou Maternity and Children's Hospital  Quanzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhu","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Quanzhou Maternity and Children's Hospital  Quanzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Lin","sequence":"additional","affiliation":[{"name":"Neonatal Disease Screening Center Quanzhou Maternity and Children's Hospital  Quanzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3921-6119","authenticated-orcid":false,"given":"Weilin","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Quanzhou Maternity and Children's Hospital  Quanzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,9]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2022.06.007"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.31162"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg-2023-109206"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12475"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijns9010006"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-021-02126-3"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2020.04.039"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-021-01785-6"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm-20-1147"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2018-0088"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0272-5"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2021.100776"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12519-022-00522-8"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2019.12.006"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029500"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12030"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12519-022-00670-x"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.686137"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00050"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,28]],"date-time":"2024-09-28T05:32:55Z","timestamp":1727501575000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9]]},"references-count":19,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/mgg3.70003"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70003","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9]]},"assertion":[{"value":"2024-04-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70003"}}