Clinical genome sequencing: three years experience at a tertiary childrens hospital

IntroductionGenome sequencing (GS) may shorten the diagnostic odyssey for patients, but clinical experience with this assay in non-research settings remains limited. Texas Childrens Hospital began offering GS as a clinical test to admitted patients in 2020, providing an opportunity to study how GS is utilized, potential for misorders, and outcomes of testing. MethodsWe conducted a retrospective review of GS orders for admitted patients for a nearly 3-year period from March 2020 through December 2022. We gathered anonymized clinical data from the electronic health record to answer the study questions. ResultsThe diagnostic yield over 97 admitted patients was 35%. The majority of GS clinical indications were neurologic or metabolic (61%) and most patients were in intensive care (58%). Tests were often characterized as misordered (56%), frequently due to redundancy with prior testing. Patients receiving GS without prior exome sequencing (ES) had higher diagnostic rates (45%) than the cohort as a whole. In two cases, GS revealed a molecular diagnosis that is unlikely to be detected by ES. ConclusionsThe performance of GS in clinical settings likely justifies its use as a first-line diagnostic test, but the incremental benefit for patients with prior ES may be limited.