Application of targeted high-throughput sequencing as a diagnostic tool for neonatal genetic metabolic diseases following tandem mass spectrometry screening
BackgroundTandem mass spectrometry (MS/MS) is a crucial technique for detecting inborn errors of metabolism (IEM) in newborns. However, the high false positive rate poses challenges in diagnosing specific types of diseases. Therefore, this study aimed to evaluate the role of targeted next-generation...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Public Health |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpubh.2024.1461141/full |
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| author | Guihua Lai Qiying Gu Zhiyong Lai Haijun Chen Xiangwen Tu Junkun Chen Jungao Huang |
| author_facet | Guihua Lai Qiying Gu Zhiyong Lai Haijun Chen Xiangwen Tu Junkun Chen Jungao Huang |
| author_sort | Guihua Lai |
| collection | DOAJ |
| description | BackgroundTandem mass spectrometry (MS/MS) is a crucial technique for detecting inborn errors of metabolism (IEM) in newborns. However, the high false positive rate poses challenges in diagnosing specific types of diseases. Therefore, this study aimed to evaluate the role of targeted next-generation sequencing (NGS) in the accurate diagnosis of positive samples identified through MS/MS screening.MethodsA cohort study of 260,915 newborns was conducted from January 2018 to June 2023 in Ganzhou City, southern China. Heel blood samples were collected within 72 h of birth and subjected to MS/MS analysis. Infants with positive MS/MS results underwent targeted NGS to confirm the diagnosis and identify genetic variants.ResultsAmong 1,265 suspected cases with positive MS/MS results, 73 were confirmed by NGS, and 12 were identified as carriers of recessive diseases. The overall incidence rate was 1 in 3,574, effectively ruling out 94.2% (1,192/1,265) of the MS/MS false-positive. We found 76 variants in 18 genes associated with 15 types of IEM. Among these, 64.47% (49/76) were pathogenic, 10.53% (8/76) were likely pathogenic. Remarkably, 7.89% (6/76) were identified as novel variants. Variants in SLC22A5 (NM_003060.4) gene was most prevalent, accounting for 41% (77/188), with hotspot variants including c.51C > G, c.1400C > G, and c.338G > A.ConclusionTargeted NGS technology can serve as a crucial diagnostic tool for neonatal genetic metabolic diseases following MS/MS screening. Additionally, we identified IEM variant hotspots and some novel variants in our region, which are the underlying causes of disease in patients with IEM. |
| format | Article |
| id | doaj-art-4606c0b9d7d14cdabcea34e6d7432dc3 |
| institution | Kabale University |
| issn | 2296-2565 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Public Health |
| spelling | doaj-art-4606c0b9d7d14cdabcea34e6d7432dc32024-12-24T06:36:45ZengFrontiers Media S.A.Frontiers in Public Health2296-25652024-12-011210.3389/fpubh.2024.14611411461141Application of targeted high-throughput sequencing as a diagnostic tool for neonatal genetic metabolic diseases following tandem mass spectrometry screeningGuihua LaiQiying GuZhiyong LaiHaijun ChenXiangwen TuJunkun ChenJungao HuangBackgroundTandem mass spectrometry (MS/MS) is a crucial technique for detecting inborn errors of metabolism (IEM) in newborns. However, the high false positive rate poses challenges in diagnosing specific types of diseases. Therefore, this study aimed to evaluate the role of targeted next-generation sequencing (NGS) in the accurate diagnosis of positive samples identified through MS/MS screening.MethodsA cohort study of 260,915 newborns was conducted from January 2018 to June 2023 in Ganzhou City, southern China. Heel blood samples were collected within 72 h of birth and subjected to MS/MS analysis. Infants with positive MS/MS results underwent targeted NGS to confirm the diagnosis and identify genetic variants.ResultsAmong 1,265 suspected cases with positive MS/MS results, 73 were confirmed by NGS, and 12 were identified as carriers of recessive diseases. The overall incidence rate was 1 in 3,574, effectively ruling out 94.2% (1,192/1,265) of the MS/MS false-positive. We found 76 variants in 18 genes associated with 15 types of IEM. Among these, 64.47% (49/76) were pathogenic, 10.53% (8/76) were likely pathogenic. Remarkably, 7.89% (6/76) were identified as novel variants. Variants in SLC22A5 (NM_003060.4) gene was most prevalent, accounting for 41% (77/188), with hotspot variants including c.51C > G, c.1400C > G, and c.338G > A.ConclusionTargeted NGS technology can serve as a crucial diagnostic tool for neonatal genetic metabolic diseases following MS/MS screening. Additionally, we identified IEM variant hotspots and some novel variants in our region, which are the underlying causes of disease in patients with IEM.https://www.frontiersin.org/articles/10.3389/fpubh.2024.1461141/fullgenetic diagnosisinborn errors of metabolismnewborn screeningtargeted sequencingtandem mass spectrometry |
| spellingShingle | Guihua Lai Qiying Gu Zhiyong Lai Haijun Chen Xiangwen Tu Junkun Chen Jungao Huang Application of targeted high-throughput sequencing as a diagnostic tool for neonatal genetic metabolic diseases following tandem mass spectrometry screening Frontiers in Public Health genetic diagnosis inborn errors of metabolism newborn screening targeted sequencing tandem mass spectrometry |
| title | Application of targeted high-throughput sequencing as a diagnostic tool for neonatal genetic metabolic diseases following tandem mass spectrometry screening |
| title_full | Application of targeted high-throughput sequencing as a diagnostic tool for neonatal genetic metabolic diseases following tandem mass spectrometry screening |
| title_fullStr | Application of targeted high-throughput sequencing as a diagnostic tool for neonatal genetic metabolic diseases following tandem mass spectrometry screening |
| title_full_unstemmed | Application of targeted high-throughput sequencing as a diagnostic tool for neonatal genetic metabolic diseases following tandem mass spectrometry screening |
| title_short | Application of targeted high-throughput sequencing as a diagnostic tool for neonatal genetic metabolic diseases following tandem mass spectrometry screening |
| title_sort | application of targeted high throughput sequencing as a diagnostic tool for neonatal genetic metabolic diseases following tandem mass spectrometry screening |
| topic | genetic diagnosis inborn errors of metabolism newborn screening targeted sequencing tandem mass spectrometry |
| url | https://www.frontiersin.org/articles/10.3389/fpubh.2024.1461141/full |
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