Development of DNA Confirmatory and High-Risk Diagnostic Testing for Newborns Using Targeted Next-Generation DNA Sequencing

Bhattacharjee, Arindam; Sokolsky, Tanya; Wyman, Stacia K.; Reese, Martin G.; Puffenberger, Erik G.; Strauss, Kevin A.; Morton, Holmes; Parad, Richard B.; Naylor, Edwin W.

doi:10.1038/gim.2014.117

Cited by 58 publications

(71 citation statements)

References 37 publications

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“…Its wider adoption is limited by long turnaround time, finding variants of unknown significance, incidental/unwanted findings such as carrier detection and the conundrum of mismatching genotype and phenotype. Some of this would be improved by choosing a newborn-specific and targeted gene panel [19].…”

Section: Discussionmentioning

confidence: 99%

Suitable Specimen Types for Newborn Biochemical Screening-A Summary

Hall¹

2017

IJNS

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Newborn biochemical screening has been in place in many countries for over fifty years initially testing dried skin puncture whole blood spotted on collection paper (DBS) or urine for phenylalanine or phenylketones to identify phenylketonuria. Countries wishing to commence newborn screening need to consider which type of specimen will provide a satisfactory specimen and matrix for testing for disorders relevant to their population, is acceptable to parents and can be readily transported to the analytical or laboratory facility without significant degradation. Whilst DBSs have largely become the specimen of choice they may not be applicable to all cultures and infrastructures. The majority of disorders appropriate to be identified in the newborn period can be detected in DBSs taken shortly after birth. Some are also detectable in cord blood or urine, some are not. Most disorders have an ideal and often different time window of age for identification in relation to treatment for optimum outcome. When embarking on newborn screening for the first time or in expanding what is already in place, it is important that the disorders considered are evaluated against the Wilson and Jungner criteria for population screening. A brief overview of specimen types including urine, cord blood and DBSs with some of their advantages and limitations is provided in this review to assist in decision-making.

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Section: Discussionmentioning

confidence: 99%

Suitable Specimen Types for Newborn Biochemical Screening-A Summary

Hall¹

2017

IJNS

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“…3 Selections of the genes and relevant mode(s) of inheritance corresponding to these conditions were based on manual review of conditions and corresponding genes listed in the Clinical Genomic Database, 15,16 Online Mendelian Inheritance in Man (OMIM), 17 and Genetics Home Reference. 18 Additional genes from work by Bhattacharjee et al, 4 were also included. Genes and conditions pertinent to the state where participating infants were born were cross-referenced with state department of health resources.…”

Section: List Of Nbs Genesmentioning

confidence: 99%

“…4,5 Despite the perceived benefits, genomic sequencing of newborns raises a number of ethical, regulatory, legal, economic, and technical issues, and the decision of whether to implement NGS as part of an NBS program requires assessment of all these factors. Some of these issues have been discussed elsewhere, such as in recent publications on ethics 6 and cost 7 of NGS for NBS.…”

Section: Introductionmentioning

confidence: 99%

Utility of whole-genome sequencing for detection of newborn screening disorders in a population cohort of 1,696 neonates

Bodian

Klein

Iyer

et al. 2016

Genetics in Medicine

110

120

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Purpose:To assess the potential of whole-genome sequencing (WGS) to replicate and augment results from conventional blood-based newborn screening (NBS). Methods:Research-generated WGS data from an ancestrally diverse cohort of 1,696 infants and both parents of each infant were analyzed for variants in 163 genes involved in disorders included or under discussion for inclusion in US NBS programs. WGS results were compared with results from state NBS and related follow-up testing.Results: NBS genes are generally well covered by WGS. There is a median of one (range: 0-6) database-annotated pathogenic variant in the NBS genes per infant. Results of WGS and NBS in detecting 28 state-screened disorders and four hemoglobin traits were concordant for 88.6% of true positives (n = 35) and 98.9% of true negatives (n = 45,757). Of the five infants affected with a state-screened disorder, WGS identified two whereas NBS detected four. WGS yielded fewer false positives than NBS (0.037 vs. 0.17%) but more results of uncertain significance (0.90 vs. 0.013%). Conclusion:WGS may help rule in and rule out NBS disorders, pinpoint molecular diagnoses, and detect conditions not amenable to current NBS assays.

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“…41 Massive parallel sequencing or next-generation sequencing is now increasingly being utilized in neonatal intensive care setting for rapid genetic diagnosis. 42,43 Collectively, the 180,000 exons (termed exome) only account for about 1.5% of the human genome, but they contribute to 80e85% of all the known disease-causative variants. Several studies have demonstrated the utility of whole exome sequencing (WES) in critically ill neonates with genetic disorders, providing prompt diagnoses for personalized care (Table 1).…”

Section: Whole Exome Sequencingmentioning

confidence: 99%

Current Genetic Testing Tools in Neonatal Medicine

Lalani

2017

Pediatrics & Neonatology

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Development of DNA Confirmatory and High-Risk Diagnostic Testing for Newborns Using Targeted Next-Generation DNA Sequencing

Cited by 58 publications

References 37 publications

Suitable Specimen Types for Newborn Biochemical Screening-A Summary

Suitable Specimen Types for Newborn Biochemical Screening-A Summary

Utility of whole-genome sequencing for detection of newborn screening disorders in a population cohort of 1,696 neonates

Current Genetic Testing Tools in Neonatal Medicine

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