Second-Tier Next Generation Sequencing Integrated in Nationwide Newborn Screening Provides Rapid Molecular Diagnostics of Severe Combined Immunodeficiency

Strand, Janne; Gul, Kiran Aftab; Erichsen, Hans Christian; Lundman, Emma; Berge, Mona C.; Trømborg, Anette K.; Sørgjerd, Linda Karlsen; Ytre-Arne, Mari; Hogner, Silje; Halsne, Ruth; Gaup, H.J.; Osnes, Liv; Kro, Grete A.B.; Sorte, Hanne Sørmo; Mørkrid, Lars; Rowe, Alexander D.; Tangeraas, Trine; Jørgensen, Jens Veilemand; Alme, Charlotte; Bjørndalen, Trude E. H.; Rønnestad, Arild; Lång, Anna; Rootwelt, Terje; Buechner, Jochen; Øverland, Torstein; Abrahamsen, Tore G.; Pettersen, Rolf D.; Stray-Pedersen, Asbjørg

doi:10.3389/fimmu.2020.01417

Cited by 43 publications

(47 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Most laboratories use commercial kits that screen for a predefined mutation panel covering the more prevalent pathogenic variants. In recent years, many pilot projects have introduced DNA analysis into NBS before the family is alerted [ 85 , 86 , 87 , 88 ]. A retrospective study conducted in Pennsylvania evaluated the feasibility of a DNA-based 2-TT, covering the most common GALT mutations (seven mutations and two variants), to improve the specificity of NBS for Galactosemia.…”

Section: Molecular Testing As a 2-ttmentioning

confidence: 99%

“…Second-tier NGS testing using DNA from the same DBS after primary screening of TRECs was proposed also for severe combined immunodeficiency and a targeted next generation approach was considered as an available second-tier approach for Pompe disease when enzymatic activity on DBS is below the established cutoff values [ 48 , 86 ]. A feasibility study to improve NBS for cystic fibrosis using NGS has been also reported [ 90 ].…”

Section: Molecular Testing As a 2-ttmentioning

confidence: 99%

See 1 more Smart Citation

Development of Strategies to Decrease False Positive Results in Newborn Screening

Malvagia

Forni

Ombrone

et al. 2020

IJNS

View full text Add to dashboard Cite

The expansion of national newborn screening (NBS) programmes has provided significant benefits in the diagnosis and early treatment of several rare, heritable conditions, preventing adverse health outcomes for most affected infants. New technological developments have enabled the implementation of testing panel covering over 50 disorders. Consequently, the increment of false positive rate has led to a high number of healthy infants recalled for expensive and often invasive additional testing, opening a debate about the harm-benefit ratio of the expanded newborn screening. The false-positive rate represents a challenge for healthcare providers working in NBS systems. Here, we give an overview on the most commonly used strategies for decreasing the adverse effects due to inconclusive screening results. The focus is on NBS performance improvement through the implementation of analytical methods, the application of new and more informative biomarkers, and by using post-analytical interpretive tools. These strategies, used as part of the NBS process, can to enhance the positive predictive value of the test and reduce the parental anxiety and healthcare costs related to the unnecessary tests and procedures.

show abstract

Section: Molecular Testing As a 2-ttmentioning

confidence: 99%

Section: Molecular Testing As a 2-ttmentioning

confidence: 99%

Development of Strategies to Decrease False Positive Results in Newborn Screening

Malvagia

Forni

Ombrone

et al. 2020

IJNS

View full text Add to dashboard Cite

show abstract

“…Muramatsu and colleagues used a similar approach, but the chromosome 22q11.2 deletion was included in the NGS panel [ 23 ]. Strand and colleagues reported a two-tier approach in a pilot NBS for SCID: the first tier consists of real-time PCR for TREC and the second-tier NGS of a targeted panel of PID-associated genes with results confirmed by Sanger sequencing [ 27 ]. This combination method allows the addition of relevant gene variant information to infants identified by TREC assays as at high risk for SCID as a part of the routine NBS process which has been demonstrated by the above cited three reports.…”

Section: Molecular Marker Identification As Primary Screening Methmentioning

confidence: 99%

Translating Molecular Technologies into Routine Newborn Screening Practice

Furnier

Durkin

Baker

2020

IJNS

View full text Add to dashboard Cite

As biotechnologies advance and better treatment regimens emerge, there is a trend toward applying more advanced technologies and adding more conditions to the newborn screening (NBS) panel. In the current Recommended Uniform Screening Panel (RUSP), all conditions but one, congenital hypothyroidism, have well-defined genes and inheritance patterns, so it is beneficial to incorporate molecular testing in NBS when it is necessary and appropriate. Indeed, the applications of molecular technologies have taken NBS to previously uncharted territory. In this paper, based on our own program experience and what has been reported in the literature, we describe current practices regarding the applications of molecular technologies in routine NBS practice in the era of genomic and precision medicine.

show abstract

“…CBS is used to confirm homocystinuria when high levels of methionine are detected by mass spectrometry. CORO1A is included in the NBS panel as it is one of the multiple genes related to severe combined immunodeficiency (SCID) 28 – 30 , and panel tested on the DNA extract when first-tier screening for SCID detects zero or low levels of T cell receptor excision circles (TRECs) by qPCR quantification 7 . The mapping results for these four genes containing the most problematic exonic regions with low mapping coverage are consistent with existing genomic data in gnomAD (.v3), which includes sequencing and mapping data from 71,702 whole genomes ( https://gnomad.broadinstitute.org/ ).…”

Section: Resultsmentioning

confidence: 99%

“…NBS programs vary by country and predominantly include testing for a range of inborn metabolic errors, endocrine disorders, primary immunodeficiency disorders, congenital deafness, congenital heart defects and cystic fibrosis 5 . Technological advances such as tandem mass spectrometry 6 and genetic sequencing 7 , 8 have thus far formed the technological basis of blood sample dependent NBS programs, and the imminence of relevant gene therapies and routine use of next-generation sequencing (NGS) in clinical laboratories means that significant opportunities for NBS have arisen.…”

Section: Introductionmentioning

confidence: 99%

Next-generation sequencing of newborn screening genes: the accuracy of short-read mapping

et al. 2020

View full text Add to dashboard Cite

Newborn screening programs are an integral part of public health systems aiming to save lives and improve the quality of life for infants with treatable disorders. Technological advancements have driven the expansion of newborn screening programs in the last two decades and the development of fast, accurate next-generation sequencing technology has opened the door to a range of possibilities in the field. However, technological challenges with short-read next-generation sequencing technologies remain significant in highly homologous genomic regions such as pseudogenes or paralogous genes and need to be considered when implemented in screening programs. Here, we simulate 50 genomes from populations around the world to test the extent to which high homology regions affect short-read mapping of genes related to newborn screening disorders and the impact of differential read lengths and ethnic backgrounds. We examine a 158 gene screening panel directly relevant to newborn screening and identify gene regions where read mapping is affected by homologous genomic regions at different read lengths. We also determine that the patient's ethnic background does not have a widespread impact on mapping accuracy or coverage. Additionally, we identify newborn screening genes where alternative forms of sequencing or variant calling pipelines should be considered and demonstrate that alterations to standard variant calling can retrieve some formerly uncalled variants.

show abstract

Second-Tier Next Generation Sequencing Integrated in Nationwide Newborn Screening Provides Rapid Molecular Diagnostics of Severe Combined Immunodeficiency

Cited by 43 publications

References 72 publications

Development of Strategies to Decrease False Positive Results in Newborn Screening

Development of Strategies to Decrease False Positive Results in Newborn Screening

Translating Molecular Technologies into Routine Newborn Screening Practice

Next-generation sequencing of newborn screening genes: the accuracy of short-read mapping

Contact Info

Product

Resources

About