Feasibility of Targeted Next-Generation DNA Sequencing for Expanding Population Newborn Screening.
BACKGROUND: Newborn screening (NBS) is an effective public health intervention that reduces death and disability from treatable genetic diseases, but many conditions are not screened due to a lack of a suitable assay. Whole genome and whole exome sequencing can potentially expand NBS but there remai...
| Publicado en: | Clinical Chemistry Vol. 69; no. 8; pp. 890 - 901 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Oxford University Press / USA
Aug2023
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=169839252&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 169839252 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00099147 10CS jtl: Clinical Chemistry issn: 00099147 maglogo: N pubinfo: dt: Aug2023 vid: 69 iid: 8 pid: 622 pub: Oxford University Press / USA artinfo: ui: 169839252 10.1093/clinchem/hvad066 169839252 ppf: 890 ppct: 11 formats: fmt: @attributes: type: P tig: atl: Feasibility of Targeted Next-Generation DNA Sequencing for Expanding Population Newborn Screening. aug: au: Oh Vic Shum, Bennett Pretorius, Carel Jacobus Min Fen Sng, Letitia Henner, Ilya Barahona, Paulette Basar, Emre McGill, Jim Wilgen, Urs Zournazi, Anna Downie, Lilian Taylor, Natalie Cheney, Liam Wu, Sylvania Twine, Natalie Angela Bauer, Denis Carolin Watts, Gerald Francis Navilebasappa, Akash Kumar, Kishore Rajagopal Ungerer, Jacobus Petrus Johannes Bennett, Glenn affil: Preventive Health Division, Genepath, Sydney, NSW, Australia sug: ab: BACKGROUND: Newborn screening (NBS) is an effective public health intervention that reduces death and disability from treatable genetic diseases, but many conditions are not screened due to a lack of a suitable assay. Whole genome and whole exome sequencing can potentially expand NBS but there remain many technical challenges preventing their use in population NBS. We investigated if targeted gene sequencing (TGS) is a feasible methodology for expanding NBS. METHODS: We constructed a TGS panel of 164 genes which screens for a broad range of inherited conditions. We designed a high-volume, low-turnaround laboratory and bioinformatics workflow that avoids the technical and data interpretation challenges associated with whole genome and whole exome sequencing. A methods-based analytical validation of the assay was completed and test performance in 2552 newborns examined. We calculated annual birth estimates for each condition to assess cost-effectiveness. RESULTS: Assay analytical sensitivity was >99% and specificity was 100%. Of the newborns screened, 1.3% tested positive for a condition. On average, each individual had 225 variants to interpret and 1.8% were variants of uncertain significance (VUS). The turnaround time was 7 to 10 days. Maximum batch size was 1536 samples. CONCLUSIONS: We demonstrate that a TGS assay could be incorporated into an NBS program soon to increase the number of conditions screened. Additionally, we conclude that NBS using TGS may be cost-effective. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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