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Updated: Jul 31, 2025
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse
Noura S Abul-Husn1, Priya N Marathe2, Nicole R Kelly3
1Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY; 23andMe, Inc., Sunnyvale, CA.
Purpose:
Adoption of genome sequencing (GS) as a first-line test requires evaluation of its diagnostic yield. We evaluated the GS and targeted gene panel (TGP) testing in diverse pediatric patients (probands) with suspected genetic conditions.
Methods:
Probands with neurologic, cardiac, or immunologic conditions were offered GS and TGP testing. Diagnostic yield was compared using a fully paired study design.
Results:
A total of 645 probands (median age 9 years) underwent genetic testing, and 113 (17.5%) received a molecular diagnosis. Among 642 probands with both GS and TGP testing, GS yielded 106 (16.5%) and TGPs yielded 52 (8.1%) diagnoses (P < .001). Yield was greater for GS vs TGPs in Hispanic/Latino(a) (17.2% vs 9.5%, P < .001) and White/European American (19.8% vs 7.9%, P < .001) but not in Black/African American (11.5% vs 7.7%, P = .22) population groups by self-report. A higher rate of inconclusive results was seen in the Black/African American (63.8%) vs White/European American (47.6%; P = .01) population group. Most causal copy number variants (17 of 19) and mosaic variants (6 of 8) were detected only by GS.
Conclusion:
GS may yield up to twice as many diagnoses in pediatric patients compared with TGP testing but not yet across all population groups.
