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Pediatric Whole Genome Sequencing Diagnostic Utility

The standard of care for first-tier clinical investigation of the etiology of congenital malformations and neurodevelopmental disorders is chromosome microarray analysis (CMA) for copy number variations (CNVs), often followed by gene(s)-specific sequencing searching for smaller insertion-deletions (indels) and single nucleotide variant (SNV) mutations. We compared diagnostic rate of WGS to CMA and targeted gene testing of 100 patients referred to The Hospital for Sick Children Genetics clinic in 2014. WGS identified genetic variants meeting clinical diagnostic criteria in 34% of cases, representing a 4-fold increase in diagnostic rate over CMA (8%) (p-value = 1.42e-05) alone and >2-fold increase in CMA plus targeted gene sequencing (13%) (p-value = 0.0009). WGS identified all rare clinically significant CNVs that were detected by CMA. In an additional 26 patients, WGS revealed indel and missense mutations presenting in a dominant (63%) or a recessive (37%) manner. We found four subjects with mutations in at least two genes associated with distinct genetic disorders, including two cases harboring a pathogenic CNV and SNV. When considering medically actionable secondary findings in addition to primary WGS findings, 38% of patients would benefit from genetic counselling.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001001856 100
Publications Citations
Whole Genome Sequencing Expands Diagnostic Utility and Improves Clinical Management in Pediatric Medicine.
NPJ Genom Med 1: 2016 15012
Genome sequencing as a platform for pharmacogenetic genotyping: a pediatric cohort study.
NPJ Genom Med 2: 2017 19
Periodic reanalysis of whole-genome sequencing data enhances the diagnostic advantage over standard clinical genetic testing.
Eur J Hum Genet 26: 2018 740-744