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Next-generation sequencing as a second-tier diagnostic test for newborn screening.

Next-generation sequencing as a second-tier diagnostic test for newborn screening.

Authors :
Luo, Xiaomei
Wang, Ruifang
Fan, Yanjie
Gu, Xuefan
Yu, Yongguo
Source :
Journal of Pediatric Endocrinology & Metabolism; Aug2018, Vol. 31 Issue 8, p927-931, 5p
Publication Year :
2018

Abstract

Background: Tandem mass spectrometry (MS/MS) has been used for newborn screening (NBS) of inherited metabolic diseases (IMDs) for decades. However, the traditional approach can yield false-positive or false-negative results and is affected by biochemical substrate-level fluctuations. To overcome the current limitations, we explored the possibility of using next-generation sequencing (NGS) as a second-tier diagnostic test to detect gene mutations in samples with abnormal MS/MS results. Methods: Genomic DNA was extracted from dried blood spots and we designed a multigene panel, comprising 77 genes related to over 40 IMDs, for NBS. The prepared libraries were sequenced on the Ion Personal Genome Machine (PGM) platform. Thirty-eight samples identified as abnormal by MS/MS were tested for the diagnostic accuracy of NGS compared with Sanger sequencing. Results: The concentration of DNA extracted from the 38 dried blood spots was sufficient for library preparation. The coverage and depth of the sequencing data were sufficient for the analysis. For all samples, the NGS results were consistent with the Sanger sequencing results. Conclusions: The genomic DNA extracted from dried blood spots could be used for NGS, generating reliable sequencing results, and NGS may function as a second-tier diagnostic test for NBS. Ion PGM could facilitate the molecular diagnosis of IMDs with appropriate primers designed for candidate genes. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0334018X
Volume :
31
Issue :
8
Database :
Supplemental Index
Journal :
Journal of Pediatric Endocrinology & Metabolism
Publication Type :
Academic Journal
Accession number :
131164155
Full Text :
https://doi.org/10.1515/jpem-2018-0088