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Which Test is Best? Evaluating the Diagnostic Yield of Sequencing-based Testing Approaches for Patients with Neurodevelopmental Disorders at a Pediatric Institution: A Retrospective Chart Review

Little, Nicholas J
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1553251181091454

Abstract Details

2019, MS, University of Cincinnati, Medicine: Genetic Counseling.
Objective: American College of Medical Genetics and Genomics (ACMG) and American Society of Human Genetics (ASHG) guidelines currently recommend targeted testing approaches for diagnostic genetic testing before pursuing whole exome sequencing (WES). However, recent literature on WES and whole genome sequencing (WGS) has suggested that WES may be equally or more effective as a first-tier sequencing test compared to traditional targeted testing approaches in certain populations. This study aimed to assess the optimal approach to genetic testing for patients with neurodevelopmental disorder (NDD) phenotypes. Clinical indications were evaluated to determine if certain indications were associated with a higher diagnostic yield. Methods: A retrospective chart review was conducted including 263 patients with NDDs who had been evaluated by a clinical geneticist at Cincinnati Children’s Hospital Medical Center (CCHMC) with WES and/or panel sequencing performed. We compared the diagnostic yield of WES and panel and described three different testing approaches: WES first (n=38), panel without WES (n=177), and panel followed by WES (n=48). Association between test results and clinical indications were evaluated. Data were analyzed using ANOVA, Kruskal-Wallis, Fisher’s exact, or the generalized estimating equation (GEE) model. Results: Overall diagnostic yield was 32%. Diagnostic yield of panel (25%) and WES first (26%) did not differ (p=1.00). Diagnostic yield of panel followed by WES was 38%, which was not a statistically significant difference compared to the 26% yield of first-tier WES (p=0.36). ICD-10 diagnostic codes for developmental delay were associated with overall increased diagnostic yield (p=0.005), while lower height percentiles were associated with increased diagnostic yield only for WES (p=0.041). Conclusions: This study indicates that there is no one superior approach to sequencing-based genetic testing in NDDs, as WES as a first or second sequencing test, and panel sequencing as the only sequencing test, were all equally effective at making a diagnosis. These data suggest that when a genetics provider is involved, there is no difference in yield between panel and WES. In clinical practice, providers deciding on an NGS testing approach may want to consider height percentile when deciding between WES and panel testing for patients with NDDs.
Melanie Myers, Ph.D. (Committee Chair)
Kathleen Collins, M.S. (Committee Member)
Emily J. (King) Partack, M.S. (Committee Member)
Leandra Tolusso, M.S. (Committee Member)
Xue Zhang, Ph.D. (Committee Member)
32 p.
Genetics
Whole Exome Sequencing; Gene Panel; Diagnostic Yield; Neurodevelopmental Disorders; Intellectual Disability; Next-generation Sequencing

Recommended Citations

Citations

  • Little, N. J. (2019). Which Test is Best? Evaluating the Diagnostic Yield of Sequencing-based Testing Approaches for Patients with Neurodevelopmental Disorders at a Pediatric Institution: A Retrospective Chart Review [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1553251181091454

    APA Style (7th edition)

  • Little, Nicholas. Which Test is Best? Evaluating the Diagnostic Yield of Sequencing-based Testing Approaches for Patients with Neurodevelopmental Disorders at a Pediatric Institution: A Retrospective Chart Review. 2019. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1553251181091454.

    MLA Style (8th edition)

  • Little, Nicholas. "Which Test is Best? Evaluating the Diagnostic Yield of Sequencing-based Testing Approaches for Patients with Neurodevelopmental Disorders at a Pediatric Institution: A Retrospective Chart Review." Master's thesis, University of Cincinnati, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1553251181091454

    Chicago Manual of Style (17th edition)

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This open access ETD is published by University of Cincinnati and OhioLINK.