Improving newborn screening for cystic fibrosis using next-generation sequencing technology: a technical feasibility study

Baker, Mei W.; Atkins, Anne; Cordovado, Suzanne K.; Hendrix, Miyono; Earley, Marie C.; Farrell, Philip M.

doi:10.1038/gim.2014.209

Cited by 83 publications

(80 citation statements)

References 30 publications

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“…If the attending physician is unaware that CF is not an ethnically linked disease, this also increases the likelihood that members of the Diaspora may be misdiagnosed 13,38 . Using next generation sequencing (NGS) to diagnose CF outperforms conventional genetic testing in terms of mutation detection rates 42 and positive predictive value 43 . One approach combined sequencing 182 of the 189 kb that constitutes CFTR with a bioinformatics pipeline that was able to identify SNPs, indels and gross rearrangements to achieve a diagnostic rate of 98.9%.…”

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confidence: 99%

Cystic Fibrosis in the African Diaspora

Stewart

Pepper

2017

Annals ATS

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Identifying mutations that cause cystic fibrosis (CF) is important for making an early, unambiguous diagnosis, which in turn is linked to better health and a greater life expectancy. In patients of African descent, a molecular diagnosis is often confounded by the fact that the majority of investigations undertaken to identify causative mutations have been conducted on European populations, and CF-causing mutations tend to be population specific. We undertook a survey of published data with the aim of identifying causative CF mutations in patients of African descent in the Americas. We found that 1,584 chromosomes had been tested in only six countries of which 876 alleles (55.3%) still remained unidentified. There were 59 mutations identified -41 of which have been shown to cause CF, 17 have no associated functional studies and one (R117H) is of varying clinical consequence. The most common mutations identified in the Diaspora were ΔF508 (29.4%; identified in America, Colombia, Brazil and Venezuela), 3120+1G>A (8.4%; identified in Brazil, America and Colombia), G85E (3.8% identified in Brazil), 1811+1.6kbA>G (3.7% identified in Colombia), and 1342-1G>C (3.1% identified in America). The majority of the mutations identified (81.4%) have been described in just one country. Our findings indicate that there is a need to fully characterise the spectrum of CF mutations in the Diaspora in order to improve diagnostic accuracy for these patients and facilitate treatment.2

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confidence: 99%

Cystic Fibrosis in the African Diaspora

Stewart

Pepper

2017

Annals ATS

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“…This will require additional studies, which will be forthcoming from both the Inova Health System group and the four groups funded through the National Institutes of Health NSIGHT program. 16 Similarly, Baker et al 19 report herein that NGS improved the diagnostic yield and provided timely refutation of false-positive results from traditional NBS for cystic fibrosis. They retrospectively examined the diagnostic utility of targeted NGS for 162 well-established cystic fibrosis-causing mutations in 165 dried blood spots from infants with abnormal immunoreactive trypsin values and with a single, non-diagnostic, heterozygous mutation upon testing with the American College of Medical Genetics and Genomics panel of 23 CFTR mutations.…”

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confidence: 85%

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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“…In addition, there are advantages to using IRT/DNA (CFTR) multi-mutation analysis, and development of such tests has proceeding rapidly [1,31]. New analytical technologies such as next generation sequencing [80] provide an opportunity to detect more than 100 CFTR mutations simultaneously within a few hours. As shown in Table 4, CF is relatively common among disorders included in newborn screening programs.…”

Section: Newborn Screening: Principles and Practicesmentioning

confidence: 99%

Translational research advances a new era of prenatal diagnosis and newborn screening

Shulman

Farrell

2018

TRD

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Abstract. This article provides a review of selected metabolic disorders resulting from genetic mutations and the methods used to identify them prenatally or facilitate diagnosis in the early neonatal period. Prenatal and neonatal diagnostic technologies have expanded and improved dramatically in the 21st century, as is their application in population-based screening and/or targeted assessment of at-risk couples. For instance, preimplantation genetic diagnosis has been a major advance. Emphasis herein has been placed on prototype diseases such as phenylketonuria, cystic fibrosis, and Tay-Sachs that have stimulated seminal efforts to improve medical practices in these fields. As more molecular strategies evolve, future developments in prenatal screening and diagnosis, along with newborn screening expansion, seem likely to continue rapid translation to the bedside.Keywords: Phenylketonuria, cystic fibrosis, Tay-Sachs disease, amniocentesis, chorionic villus sampling, tandem mass spectrometry Metabolic disorders resulting from genetic mutations have challenged obstetricians and pediatricians to develop diagnostic methods to identify them prenatally or in the early neonatal period [1]. The strategy of translational research has been ideal to close this gap as biotechnological advances are applied from the stage of novel laboratory developments to the practice of maternal-fetal medicine and neonatology. Although prenatal and neonatal diagnostic technologies have evolved gradually over four decades, they are expanding and changing dramatically in the 21st century, as is their application in population-based screening and/or targeted assessment of at-risk couples [1]. These changes have resulted in part from the Human Genome Project, a multicenter project supported by public and private funding geared to the sequencing of the human genome, which was completed in 2003. Clearly, the demand for prenatal genetic screening testing will continue as a result of individual and organizational advocacy efforts. In addition, advances in analytical technologies applying sophisticated cellular and molecular biology methods have increased the number and quality of tests available. Therefore, we are providing an overview with emphasis on prenatal diagnosis and suggest more comprehensive references in the bibliography [2][3][4][5]. We also recommend that the reader consult practice guidelines publications of

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Improving newborn screening for cystic fibrosis using next-generation sequencing technology: a technical feasibility study

Cited by 83 publications

References 30 publications

Cystic Fibrosis in the African Diaspora

Cystic Fibrosis in the African Diaspora

Newborn testing and screening by whole-genome sequencing

Translational research advances a new era of prenatal diagnosis and newborn screening

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