Incorporating Next-Generation Sequencing as a Second-Tier Test for Primary Carnitine Deficiency.

Autor: Lin Y; Department of Clinical Laboratory, Quanzhou Maternity and Children's Hospital, Quanzhou, Fujian, China., Zheng Z; Department of Clinical Laboratory, Quanzhou Maternity and Children's Hospital, Quanzhou, Fujian, China., Lin W; Neonatal Disease Screening Center, Quanzhou Maternity and Children's Hospital, Quanzhou, Fujian, China., Peng W; Department of Clinical Laboratory, Quanzhou Maternity and Children's Hospital, Quanzhou, Fujian, China.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2024 Sep; Vol. 12 (9), pp. e70003.
DOI: 10.1002/mgg3.70003
Abstrakt: Background: Newborn screening (NBS) for primary carnitine deficiency (PCD) has poor performance. This study aimed to evaluate the feasibility of incorporating next-generation sequencing (NGS) as a second-tier PCD test.
Methods: Between March and December 2020, 60,070 newborns were screened for inherited metabolic disorders. Newborns with free carnitine (C0) levels below 8.5 μmol/L were selected for second-tier genetic testing.
Results: In total, 130 (0.22%) newborns with low C0 levels underwent second-tier genetic testing, 87 (66.92%) had positive genetic testing results, and 30 (23.08%) carried pathogenic variants of the SLC22A5 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-tier NGS. Of the eight variants identified in patients with PCD, the three most common variants were c.760C>T (p.Arg254*), c.51C>G (p.Phe17Leu), and c.1400C>G (p.Ser467Cys). The C0 levels of patients with PCD were significantly lower than those of PCD carriers (p = 0.0026) and PCD-negative individuals (p = 0.0005).
Conclusions: Our results showed that the PPV reached 20% after combining with second-tier NGS. The MS/MS-based NBS and second-tier NGS combination can effectively reduce the false-positive rate and detect PCD in patients.
(© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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