A New Integrated Newborn Screening Workflow Can Provide a Shortcut to Differential Diagnosis and Confirmation of Inherited Metabolic Diseases.
10.3349/ymj.2018.59.5.652
- Author:
Jung Min KO
1
;
Kyung Sun PARK
;
Yeeok KANG
;
Seong Hyeuk NAM
;
Yoonjung KIM
;
Inho PARK
;
Hyun Wook CHAE
;
Soon Min LEE
;
Kyung A LEE
;
Jong Won KIM
Author Information
1. Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Newborn screening;
inherited metabolic disease;
dried blood spot;
targeted gene panel sequencing;
next-generation sequencing
- MeSH:
Alleles;
Diagnosis;
Diagnosis, Differential*;
Humans;
Infant, Newborn*;
Mass Screening*;
Metabolic Diseases*;
Molecular Biology;
Pilot Projects
- From:Yonsei Medical Journal
2018;59(5):652-661
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
