Perspectives on Next-Generation Newborn Screening

Park, Kyoung-Jin; Kim, Jong Won

doi:10.3343/lmo.2015.5.4.169

Cited by 2 publications

(3 citation statements)

References 18 publications

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“…However, only 6 IMDs (congenital hypothyroidism, congenital adrenal hyperplasia, phenylketonuria, maple syrup urine disease, galactosemia, and homocystinuria) have been performed free of charge by the government and other IMDs are not financially covered by the government. 1 Traditionally, abnormal NBS result warrants differential diagnosis of the suspected disease, based on an analysis of specific enzymatic or biochemical features in the blood or urine specimens ( Fig. 1A ).…”

Section: Introductionmentioning

confidence: 99%

A New Integrated Newborn Screening Workflow Can Provide a Shortcut to Differential Diagnosis and Confirmation of Inherited Metabolic Diseases

Park

Kang

et al. 2018

Yonsei Med J

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PurposeWe developed a new workflow design which included results from both biochemical and targeted gene sequencing analysis interpreted comprehensively. We then conducted a pilot study to evaluate the benefit of this new approach in newborn screening (NBS) and demonstrated the efficiency of this workflow in detecting causative genetic variants.Materials and MethodsTen patients in Group 1 were diagnosed clinically using biochemical assays only, and 10 newborns in Group 2 were diagnosed with suspected inherited metabolic disease (IMD) in NBS. We applied NewbornDiscovery (SD Genomics), an integrated workflow design that encompasses analyte-phenotype-gene, single nucleotide variant/small insertion and deletion/copy number variation analyses along with clinical interpretation of genetic variants related to each participant's condition.ResultsA molecular genetic diagnosis was established in 95% (19/20) of individuals. In Group 1, 13 and 7 of 20 alleles were classified as pathogenic and likely pathogenic, respectively. In Group 2, 11 and 6 of 17 alleles with identified causative variants were pathogenic and likely pathogenic, respectively. There were no variants of uncertain significance. For each individual, the NewbornDiscovery and biochemical analysis results reached 100% concordance, since the single newborn testing negative for causative genetic variant in Group 2 showed a benign clinical course.ConclusionThis integrated diagnostic workflow resulted in a high yield. This approach not only enabled early confirmation of specific IMD, but also detected conditions not included in the current NBS.

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Section: Introductionmentioning

confidence: 99%

A New Integrated Newborn Screening Workflow Can Provide a Shortcut to Differential Diagnosis and Confirmation of Inherited Metabolic Diseases

Park

Kang

et al. 2018

Yonsei Med J

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“…Over the past decade, tandem mass spectrometry (MS/MS) has been a major technological breakthrough for the NBS program by providing a way to detect multiple metabolites simultaneously [ 3 4 5 6 7 ]. Although the use of MS/MS has enabled cost-effective, rapid IMD identification, there have been some bottlenecks such as false-positives and imprecision [ 4 5 6 8 ]. As a second-tier method, enzymatic assays are laborious, time-consuming, and semiquantitative.…”

Section: Introductionmentioning

confidence: 99%

“…As a second-tier method, enzymatic assays are laborious, time-consuming, and semiquantitative. Sequential Sanger sequencing is hampered by the genetic heterogeneity of IMDs, which results in delayed diagnosis [ 8 9 ]. These limitations of the current NBS tests have raised a necessity of rapidly diagnosing IMDs by next-generation sequencing (NGS) [ 8 9 10 11 12 ].…”

Section: Introductionmentioning

confidence: 99%

A Population-Based Genomic Study of Inherited Metabolic Disaeases Detected Through Newborn Screening

Park

Lee

et al. 2016

Ann Lab Med

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BackgroundA newborn screening (NBS) program has been utilized to detect asymptomatic newborns with inherited metabolic diseases (IMDs). There have been some bottlenecks such as false-positives and imprecision in the current NBS tests. To overcome these issues, we developed a multigene panel for IMD testing and investigated the utility of our integrated screening model in a routine NBS environment. We also evaluated the genetic epidemiologic characteristics of IMDs in a Korean population.MethodsIn total, 269 dried blood spots with positive results from current NBS tests were collected from 120,700 consecutive newborns. We screened 97 genes related to NBS in Korea and detected IMDs, using an integrated screening model based on biochemical tests and next-generation sequencing (NGS) called NewbornSeq. Haplotype analysis was conducted to detect founder effects.ResultsThe overall positive rate of IMDs was 20%. We identified 10 additional newborns with preventable IMDs that would not have been detected prior to the implementation of our NGS-based platform NewbornSeq. The incidence of IMDs was approximately 1 in 2,235 births. Haplotype analysis demonstrated founder effects in p.Y138X in DUOXA2, p.R885Q in DUOX2, p.Y439C in PCCB, p.R285Pfs*2 in SLC25A13, and p.R224Q in GALT.ConclusionsThrough a population-based study in the NBS environment, we highlight the screening and epidemiological implications of NGS. The integrated screening model will effectively contribute to public health by enabling faster and more accurate IMD detection through NBS. This study suggested founder mutations as an explanation for recurrent IMD-causing mutations in the Korean population.

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Perspectives on Next-Generation Newborn Screening

Cited by 2 publications

References 18 publications

A New Integrated Newborn Screening Workflow Can Provide a Shortcut to Differential Diagnosis and Confirmation of Inherited Metabolic Diseases

A New Integrated Newborn Screening Workflow Can Provide a Shortcut to Differential Diagnosis and Confirmation of Inherited Metabolic Diseases

A Population-Based Genomic Study of Inherited Metabolic Disaeases Detected Through Newborn Screening

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