A New Integrated Newborn Screening Workflow Can Provide a Shortcut to Differential Diagnosis and Confirmation of Inherited Metabolic Diseases
Yonsei Medical Journal
; : 652-661, 2018.
Article
en En
| WPRIM
| ID: wpr-715897
Biblioteca responsable:
WPRO
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 ANDMETHODS:
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.Palabras clave
Texto completo:
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Índice:
WPRIM
Asunto principal:
Proyectos Piloto
/
Tamizaje Masivo
/
Diagnóstico
/
Diagnóstico Diferencial
/
Alelos
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Enfermedades Metabólicas
/
Biología Molecular
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Límite:
Humans
/
Newborn
Idioma:
En
Revista:
Yonsei Medical Journal
Año:
2018
Tipo del documento:
Article