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KMID : 0311120180590050652
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Yonsei Medical Journal
2018 Volume.59 No. 5 p.652 ~ p.661
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A New Integrated Newborn Screening Workflow Can Provide a Shortcut to Differential Diagnosis and Confirmation of Inherited Metabolic Diseases
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Ko Jung-Min
Park Kyung-Sun
Kang Yee-Ok
Nam Seong-Hyeuk
Kim Yoon-Jung
Park In-Ho
Chae Hyun-Wook
Lee Soon-Min
Lee Kyung-A
Kim Jong-Won
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Abstract
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Purpose: We 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 Methods: Ten 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.
Results: A 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.
Conclusion: This 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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KEYWORD
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Newborn screening, inherited metabolic disease, dried blood spot, targeted gene panel sequencing, next-generation sequencing
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