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Genet Med. 2015 May;17(5):337-47. doi: 10.1038/gim.2014.117. Epub 2014 Sep 25.

Development of DNA confirmatory and high-risk diagnostic testing for newborns using targeted next-generation DNA sequencing.

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Parabase Genomics, Boston, Massachusetts, USA.
Omicia, Oakland, California, USA.
Clinic for Special Children, Strasburg, Pennsylvania, USA.
Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
1] Parabase Genomics, Boston, Massachusetts, USA [2] Division of Genetics, Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, USA.



Genetic testing is routinely used for second-tier confirmation of newborn sequencing results to rule out false positives and to confirm diagnoses in newborns undergoing inpatient and outpatient care. We developed a targeted next-generation sequencing panel coupled with a variant processing pipeline and demonstrated utility and performance benchmarks across multiple newborn disease presentations in a retrospective clinical study.


The test utilizes an in silico gene filter that focuses directly on 126 genes related to newborn screening diseases and is applied to the exome or a next-generation sequencing panel called NBDx. NBDx targets the 126 genes and additional newborn-specific disorders. It integrates DNA isolation from minimally invasive biological specimens, targeted next-generation screening, and rapid characterization of genetic variation.


We report a rapid parallel processing of 8 to 20 cases within 105 hours with high coverage on our NBDx panel. Analytical sensitivity of 99.8% was observed across known mutation hotspots. Concordance calls with or without clinical summaries were 94% and 75%, respectively.


Rapid, automated targeted next-generation sequencing and analysis are practical in newborns for second-tier confirmation and neonatal intensive care unit diagnoses, laying a foundation for future primary DNA-based molecular screening of additional disorders and improving existing molecular testing options for newborns.

[Indexed for MEDLINE]

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