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

Bodian, Dale L.; Klein, Elisabeth; Iyer, Ramaswamy K.; Wong, Wendy S. W.; Kothiyal, Prachi; Stauffer, Daniel; Huddleston, Kathi; Gaither, Amber D.; Remsburg, Irina; Khromykh, Alina; Baker, Robin; Maxwell, G. Larry; Vockley, Joseph G.; Niederhuber, John E.; Solomon, Benjamin D.

doi:10.1038/gim.2015.111

Cited by 120 publications

(130 citation statements)

References 31 publications

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“…The SFWG hopes this process of nominations and updates will serve as a reference point in related efforts, such as initiatives that apply genetic and genomic testing in public health programs and population screening. Successful efforts have already been directed toward evaluating the efficacy of newborn screening panels in detecting genetic diseases, 21,22 and a similar approach could begin to evaluate the utility of certain applications of genomic screening in healthy adults. The reporting of SFs presents significant opportunities to prevent disease, but this process may introduce fiscal and other costs, including those associated with further confirmatory testing.…”

Section: Assessing the Impact Of Secondary Findingsmentioning

confidence: 99%

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics

Kalia

Adelman

Bale³

et al. 2017

Genetics in Medicine

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Section: Assessing the Impact Of Secondary Findingsmentioning

confidence: 99%

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics

Kalia

Adelman

Bale³

et al. 2017

Genetics in Medicine

1,500

1,377

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“…Pushing this envelope, a recent study has compared the results of standard newborn screening, which is typically performed within 48 h of birth, to exome sequencing, although this is not yet feasible on a population scale. 1 Additional studies are underway to further this comparison and to analyze the ethical, legal, and social implications of such testing in a newborn population. [2][3][4] Clinical exome sequencing, removed from the newborn screening setting, relies on a combination of accurate clinical information submitted by the ordering provider and careful variant interpretation from the reporting laboratory.…”

Section: Introductionmentioning

confidence: 99%

Variants of uncertain significance in newborn screening disorders: implications for large-scale genomic sequencing

Narravula

Garber

Askree

et al. 2017

Genetics in Medicine

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“…Thus, the results of the study by Bodian et al, 18 reported herein, will be of broad interest to readers of Genetics in Medicine. In the first prospective study of its kind, they compared the relative diagnostic yield of traditional NBS with NBS-by-WGS for 65 genes in 1,696 predominantly healthy newborns.…”

Section: Commentarymentioning

confidence: 57%

Newborn testing and screening by whole-genome sequencing

Kingsmore

2016

Genetics in Medicine

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Over the course of the next few decades, the availability of cheap, efficient DNA sequencing technology will lead to a medical landscape in which each baby's genome is sequenced, and that information is used to shape a lifetime of personalized strategies for disease prevention, detection, and treatment. -Francis Collins 1When the helmsman of the world's leading supporter of biomedical research declares that large-scale newborn genome sequencing is on the horizon and will transform medicine, it behooves health-care researchers, practitioners, and leaders to pay close attention. Thus, to introduce this themed issue on newborn diagnostic testing and newborn screening (NBS) by next-generation sequencing (NGS), I briefly summarize progress and trends in this area of imminent great change.In the past 18 months there have been remarkable improvements in methods for whole-genome sequencing (WGS). Most notable was the introduction of a new range of Illumina sequencing instruments with patterned flow cells. These instruments allow 18,000 genomes per year to be robustly sequenced at a cost of $1,000 each. 2 Together with improved software for read alignment and variant calling, these instruments have increased the analytic sensitivity and specificity of WGS for nucleotide variants to greater than 99.5%. 3 In parallel, Complete Genomics is in the process of a commercial launch of a sequencing system that enables WGS of 10,000 genomes per year, at a similar cost. 4 Concomitantly, there have been significant advances in the quality, functionality, and availability of commercial software and freeware for WGS analysis and interpretation, and of reference and pathogenic variant databases, such that interpretation and reporting are now scalable to large numbers of patients. Thus, for the first time, WGS of the 3.9 million babies born in the United States each year will be technically feasible in 2016. It is likely to be Qatar, and not the United States, however, that will be the first to undertake population-scale newborn WGS. 5 Single-gene diseases, which now number an astonishing 8,042, are the leading cause of death in infants and in those in neonatal (NICUs) and pediatric intensive care units (PICUs) in the United States. 6 Thus, it is not surprising that one of the first applications in which WGS has shown diagnostic utility is in NICU infants. 7,8 For acute clinical utility in the NICU or PICU, however, WGS must be capable of returning results much faster than in a typical research or reference laboratory setting. Indeed, in a recent case series, 57% of regional (level IV) NICU babies diagnosed with genetic diseases had died by day of life 100. 7 In response, rapid WGS methods have been developed specifically for timely genetic disease diagnosis in the NICU and PICU. 3,9-11 The current speed record is 26 h from neonatologist referral to return of a provisional diagnosis. 3 In the same case series, the diagnostic rate of WGS was 57%, a figure higher than that obtained in other clinical settings. 7,8,[12][13][14][15] To date,...

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

Cited by 120 publications

References 31 publications

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics

Variants of uncertain significance in newborn screening disorders: implications for large-scale genomic sequencing

Newborn testing and screening by whole-genome sequencing

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