Diagnostic Rates of Rapid Exome Sequencing in Critical Settings

Introduction: Undiagnosed genetic diseases are one of the leading causes of infant morbidity and mortality, and can be a significant public health concern for both providers and patients alike. In a critical care setting, rapid and comprehensive genetic testing needs to be considered for patients to achieve equitable care. As Whole Exome Sequencing (WES) has slowly become the standard of care for many clinically complex patients, Rapid Whole Exome Sequencing (rWES) is quickly becoming a first step for many infants and children with acute medical issues in an inpatient setting. Methods: Using data collected from 2015 to 2021 from a large clinical genetics laboratory, GeneDx, results from rWES were reviewed and the diagnostic rate was established. The diagnostic rate was stratified by the number of samples submitted for testing, clinical indication, age of the proband, and inclusion of mitochondrial genome sequencing and deletion/duplication studies (mtDNA) and the associated results. The significance of the results was assessed by the chi-squared statistical test. Results: 2744 rWES cases were retrospectively reviewed and evaluated for the diagnostic rate . The overall diagnostic yield of rWES in this cohort is 33 .3%. Comparing Trios and Non-Trios, the diagnostic yield differs greatly with Trio cases having a diagnostic yield of 35.5% and Non-Trios a yield of 20% (p-value