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Clinical exome sequencing by general pediatricians: high clinical utility and no evidence of inappropriate testing
Danya Salah Baz1, Dareen Baz1, Fawzah Alrwuili2
1College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
Insights
General pediatricians can effectively order clinical exome sequencing (CES) for diagnosing genetic disorders in children. This approach offers significant clinical utility and diagnostic yield, improving patient access to genetic testing.
Area of Science:
- Medical Genetics
- Pediatric Diagnostics
- Genomic Medicine
Background:
- Genetic disorders are a major cause of pediatric hospital admissions.
- Clinical exome sequencing (CES) is underutilized by general pediatricians.
- Direct ordering of CES by pediatricians can improve access to diagnostics.
Purpose of the Study:
- To evaluate the appropriateness and clinical utility of CES ordered by general pediatricians.
- To assess the diagnostic yield and impact of CES on patient management.
- To identify barriers for pediatricians in ordering CES.
Main Methods:
- Retrospective review of 30 CES cases ordered by general pediatricians (2019-2023).
- Assessment of indications, results, and clinical utility through pediatrician interviews.
- Evaluation of changes in management, communication, subsequent testing, and counseling.
Main Results:
- CES was appropriately indicated in 100% of cases.
- Positive findings (pathogenic/likely pathogenic variants) occurred in 37% of cases.
- Clinical utility was confirmed in all positive cases, with reproductive counseling being significant.
Conclusions:
- CES ordered by general pediatricians demonstrates appropriate indication and diagnostic yield comparable to specialists.
- Positive CES results have high clinical utility, impacting patient management and counseling.
- Empowering pediatricians to order CES can shorten the diagnostic odyssey for children with genetic disorders.
Background:
Genetic disorders account for a large percentage of admissions and outpatient visits to children's hospitals around the world. Clinical exome sequencing (CES) is a valuable diagnostic tool in the workup of these disorders; however, it is not routinely requested by general pediatricians. This may represent a missed opportunity to increase patient access to this powerful diagnostic tool. In our institution, general pediatricians can directly order CES. In this context, this study aims to evaluate the appropriateness of CES and its clinical utility when ordered by general pediatricians.
Methods:
We retrospectively reviewed all CES tests ordered by general pediatricians in our institution between 2019 and 2023 and recorded their indications and results. General pediatricians were interviewed to evaluate how CES impacted the domains of clinical utility by assessing changes in management, communication, subsequent testing, and counseling. In addition, feedback was obtained, and barriers faced by general pediatricians to order CES were assessed.
Results:
The study cohort (n = 30) included children from the inpatient (60%) and outpatient (40%) departments. A positive finding (a pathogenic or likely pathogenic variant that explains the phenotype) was observed in 11 of 30 cases (37%), while 3 (10%) and 16 (53%) received ambiguous (variant of uncertain significance) and negative results, respectively. The indication was deemed appropriate in all 30 cases (100%). Clinical utility was reported in all 11 positive cases (100%). Reproductive counseling is a notable utility in this highly consanguineous population, as all variants identified, in the 11 positive cases, were autosomal recessive.
Conclusion:
We show that CES ordered by general pediatricians is appropriately indicated and provides a diagnostic yield comparable to that requested by specialists. In addition, we note the high clinical utility of positive results as judged by the ordering pediatricians. The findings of this study can empower general pediatricians to advocate for expanded CES adoption to improve patient access and shorten their diagnostic odyssey.
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