Towards Next-Generation Sequencing (NGS)-Based Newborn Screening: A Technical Study to Prepare for the Challenges Ahead
Newborn screening (NBS) aims to identify neonates with severe conditions for whom immediate treatment is required. Currently, a biochemistry-first approach is used to identify these disorders, which are predominantly inherited meta1bolic disorders (IMD). Next-generation sequencing (NGS) is expected...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | International Journal of Neonatal Screening |
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| Online Access: | https://www.mdpi.com/2409-515X/8/1/17 |
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| author | Abigail Veldman Mensiena B. G. Kiewiet Margaretha Rebecca Heiner-Fokkema Marcel R. Nelen Richard J. Sinke Birgit Sikkema-Raddatz Els Voorhoeve Dineke Westra Martijn E. T. Dollé Peter C. J. I. Schielen Francjan J. van Spronsen |
| author_facet | Abigail Veldman Mensiena B. G. Kiewiet Margaretha Rebecca Heiner-Fokkema Marcel R. Nelen Richard J. Sinke Birgit Sikkema-Raddatz Els Voorhoeve Dineke Westra Martijn E. T. Dollé Peter C. J. I. Schielen Francjan J. van Spronsen |
| author_sort | Abigail Veldman |
| collection | DOAJ |
| description | Newborn screening (NBS) aims to identify neonates with severe conditions for whom immediate treatment is required. Currently, a biochemistry-first approach is used to identify these disorders, which are predominantly inherited meta1bolic disorders (IMD). Next-generation sequencing (NGS) is expected to have some advantages over the current approach, for example the ability to detect IMDs that meet all screening criteria but lack an identifiable biochemical footprint. We have now designed a technical study to explore the use of NGS techniques as a first-tier approach in NBS. Here, we describe the aim and set-up of the NGS-first for the NBS (NGSf4NBS) project, which will proceed in three steps. In Step 1, we will identify IMDs eligible for NGS-first testing, based on treatability. In Step 2, we will investigate the feasibility, limitations and comparability of different technical NGS approaches and analysis workflows for NBS, eventually aiming to develop a rapid NGS-based workflow. Finally, in Step 3, we will prepare for the incorporation of this workflow into the existing Dutch NBS program and propose a protocol for referral of a child after a positive NGS test result. The results of this study will be the basis for an additional analytical route within NBS that will be further studied for its applicability within the NBS program, e.g., regarding the ethical, legal, financial and social implications. |
| first_indexed | 2024-03-09T19:40:05Z |
| format | Article |
| id | doaj.art-0a81dc6ddb1e489aa423fa9769bfe43a |
| institution | Directory Open Access Journal |
| issn | 2409-515X |
| language | English |
| last_indexed | 2024-03-09T19:40:05Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Neonatal Screening |
| spelling | doaj.art-0a81dc6ddb1e489aa423fa9769bfe43a2023-11-24T01:39:42ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2022-02-01811710.3390/ijns8010017Towards Next-Generation Sequencing (NGS)-Based Newborn Screening: A Technical Study to Prepare for the Challenges AheadAbigail Veldman0Mensiena B. G. Kiewiet1Margaretha Rebecca Heiner-Fokkema2Marcel R. Nelen3Richard J. Sinke4Birgit Sikkema-Raddatz5Els Voorhoeve6Dineke Westra7Martijn E. T. Dollé8Peter C. J. I. Schielen9Francjan J. van Spronsen10Division of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDivision of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Human Genetics, Radboud University Medical Center, 6500 HB Nijmegen, The NetherlandsDepartment of Genetics, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Genetics, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsCentre for Health Protection, National Institute for Public Health and the Environment, 3720 BA Bilthoven, The NetherlandsDepartment of Human Genetics, Radboud University Medical Center, 6500 HB Nijmegen, The NetherlandsCentre for Health Protection, National Institute for Public Health and the Environment, 3720 BA Bilthoven, The NetherlandsCentre for Population Screening, National Institute for Public Health and the Environment, 3720 BA Bilthoven, The NetherlandsDivision of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsNewborn screening (NBS) aims to identify neonates with severe conditions for whom immediate treatment is required. Currently, a biochemistry-first approach is used to identify these disorders, which are predominantly inherited meta1bolic disorders (IMD). Next-generation sequencing (NGS) is expected to have some advantages over the current approach, for example the ability to detect IMDs that meet all screening criteria but lack an identifiable biochemical footprint. We have now designed a technical study to explore the use of NGS techniques as a first-tier approach in NBS. Here, we describe the aim and set-up of the NGS-first for the NBS (NGSf4NBS) project, which will proceed in three steps. In Step 1, we will identify IMDs eligible for NGS-first testing, based on treatability. In Step 2, we will investigate the feasibility, limitations and comparability of different technical NGS approaches and analysis workflows for NBS, eventually aiming to develop a rapid NGS-based workflow. Finally, in Step 3, we will prepare for the incorporation of this workflow into the existing Dutch NBS program and propose a protocol for referral of a child after a positive NGS test result. The results of this study will be the basis for an additional analytical route within NBS that will be further studied for its applicability within the NBS program, e.g., regarding the ethical, legal, financial and social implications.https://www.mdpi.com/2409-515X/8/1/17next-generation sequencingfirst-tierheel prickdried blood spotinherited metabolic disordersinborn errors of metabolism |
| spellingShingle | Abigail Veldman Mensiena B. G. Kiewiet Margaretha Rebecca Heiner-Fokkema Marcel R. Nelen Richard J. Sinke Birgit Sikkema-Raddatz Els Voorhoeve Dineke Westra Martijn E. T. Dollé Peter C. J. I. Schielen Francjan J. van Spronsen Towards Next-Generation Sequencing (NGS)-Based Newborn Screening: A Technical Study to Prepare for the Challenges Ahead International Journal of Neonatal Screening next-generation sequencing first-tier heel prick dried blood spot inherited metabolic disorders inborn errors of metabolism |
| title | Towards Next-Generation Sequencing (NGS)-Based Newborn Screening: A Technical Study to Prepare for the Challenges Ahead |
| title_full | Towards Next-Generation Sequencing (NGS)-Based Newborn Screening: A Technical Study to Prepare for the Challenges Ahead |
| title_fullStr | Towards Next-Generation Sequencing (NGS)-Based Newborn Screening: A Technical Study to Prepare for the Challenges Ahead |
| title_full_unstemmed | Towards Next-Generation Sequencing (NGS)-Based Newborn Screening: A Technical Study to Prepare for the Challenges Ahead |
| title_short | Towards Next-Generation Sequencing (NGS)-Based Newborn Screening: A Technical Study to Prepare for the Challenges Ahead |
| title_sort | towards next generation sequencing ngs based newborn screening a technical study to prepare for the challenges ahead |
| topic | next-generation sequencing first-tier heel prick dried blood spot inherited metabolic disorders inborn errors of metabolism |
| url | https://www.mdpi.com/2409-515X/8/1/17 |
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