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

 Jung Min Ko  ;  Kyung Sun Park  ;  Yeeok Kang  ;  Seong Hyeuk Nam  ;  Yoonjung Kim  ;  Inho Park  ;  Hyun Wook Chae  ;  Soon Min Lee  ;  Kyung A Lee  ;  Jong Won Kim 
 YONSEI MEDICAL JOURNAL, Vol.59(5) : 652-661, 2018 
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Alleles ; *Computational Biology ; DNA Copy Number Variations ; Differential *Diagnosis ; Dried Blood Spot Testing ; Female ; Genetic Testing/*methods ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Newborn Infant ; Male ; Metabolic Diseases/*diagnosis/genetics ; *Neonatal Screening ; Pilot Projects ; DNA Sequence Analysis ; Workflow
Newborn screening ; dried blood spot ; inherited metabolic disease ; next-generation sequencing ; targeted gene panel sequencing
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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1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Kyung A(이경아) ORCID logo https://orcid.org/0000-0001-5320-6705
Lee, Soon Min(이순민) ORCID logo https://orcid.org/0000-0003-0174-1065
Chae, Hyun Wook(채현욱) ORCID logo https://orcid.org/0000-0001-5016-8539
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