Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Aug 3:3:67.
doi: 10.3389/fped.2015.00067. eCollection 2015.

Clinical Impact and Cost-Effectiveness of Whole Exome Sequencing as a Diagnostic Tool: A Pediatric Center's Experience

C Alexander Valencia  1 , Ammar Husami  1 , Jennifer Holle  1 , Judith A Johnson  1 , Yaping Qian  2 , Abhinav Mathur  1 , Chao Wei  1 , Subba Rao Indugula  1 , Fanggeng Zou  1 , Haiying Meng  1 , Lijun Wang  1 , Xia Li  1 , Rachel Fisher  1 , Tony Tan  1 , Amber Hogart Begtrup  1 , Kathleen Collins  1 , Katie A Wusik  1 , Derek Neilson  1 , Thomas Burrow  1 , Elizabeth Schorry  1 , Robert Hopkin  1 , Mehdi Keddache  1 , John Barker Harley  3 , Kenneth M Kaufman  3 , Kejian Zhang  1
Affiliations

Clinical Impact and Cost-Effectiveness of Whole Exome Sequencing as a Diagnostic Tool: A Pediatric Center's Experience

C Alexander Valencia et al. Front Pediatr. .

Abstract

Background: There are limited reports of the use of whole exome sequencing (WES) as a clinical diagnostic tool. Moreover, there are no reports addressing the cost burden associated with genetic tests performed prior to WES.

Objective: We demonstrate the performance characteristics of WES in a pediatric setting by describing our patient cohort, calculating the diagnostic yield, and detailing the patients for whom clinical management was altered. Moreover, we examined the potential cost-effectiveness of WES by examining the cost burden of diagnostic workups.

Methods: To determine the clinical utility of our hospital's clinical WES, we performed a retrospective review of the first 40 cases. We utilized dual bioinformatics analyses pipelines based on commercially available software and in-house tools.

Results: Of the first 40 clinical cases, we identified genetic defects in 12 (30%) patients, of which 47% of the mutations were previously unreported in the literature. Among the 12 patients with positive findings, seven have autosomal dominant disease and five have autosomal recessive disease. Ninety percent of the cohort opted to receive secondary findings and of those, secondary medical actionable results were returned in three cases. Among these positive cases, there are a number of novel mutations that are being reported here. The diagnostic workup included a significant number of genetic tests with microarray and single-gene sequencing being the most popular tests. Significantly, genetic diagnosis from WES led to altered patient medical management in positive cases.

Conclusion: We demonstrate the clinical utility of WES by establishing the clinical diagnostic rate and its impact on medical management in a large pediatric center. The cost-effectiveness of WES was demonstrated by ending the diagnostic odyssey in positive cases. Also, in some cases it may be most cost-effective to directly perform WES. WES provides a unique glimpse into the complexity of genetic disorders.

Keywords: children; clinical utility; diagnosis; next generation sequencing; pediatrics; whole exome sequencing.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Descriptive statistics of the patient cohort and the positive exome cases.
Figure 2
Figure 2
Genetic testing cost analysis of cohort prior to whole exome sequencing. (A) Number of genetic tests performed before whole exome sequencing per patient. (B) Types of genetic tests completed in the cohort prior to whole exome sequencing.
See this image and copyright information in PMC

References

    1. McCandless SE, Brunger JW, Cassidy SB. The burden of genetic disease on inpatient care in a children’s hospital. Am J Hum Genet (2004) 74:121–7.10.1086/381053 - DOI - PMC - PubMed
    1. Gahl WA, Markello TC, Toro C, Fajardo KF, Sincan M, Gill F, et al. The national institutes of health undiagnosed diseases program: insights into rare diseases. Genet Med (2012) 14:51–9.10.1038/gim.0b013e318232a005 - DOI - PMC - PubMed
    1. Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature (2009) 461:272–6.10.1038/nature08250 - DOI - PMC - PubMed
    1. Lupski JR, Reid JG, Gonzaga-Jauregui C, Rio Deiros D, Chen DCY, Nazareth L, et al. Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. N Engl J Med (2010) 362:1181–91.10.1056/NEJMoa0908094 - DOI - PMC - PubMed
    1. Vissers LELM, de Ligt J, Gilissen C, Janssen I, Steehouwer M, de Vries P, et al. A de novo paradigm for mental retardation. Nat Genet (2010) 42:1109–12.10.1038/ng.712 - DOI - PubMed