This is a prospective, multi-site, non-randomized (single arm) study to evaluate the feasibility, the yield and clinical utility of trio WGS in critically ill patients in neonatology intensive care units (NICU) and pediatric intensive care units (PICU) in Belgium. Each proband responding to our eligibility criteria will receive a trio WGS.~Blood samples from enrolled probands and their parents will be collected and shipped to the Laboratoire de Génétique Humaine, University of Liège, Liège, Belgium, which is a research facility. Blood samples will be lysed using the Illumina Lysis Kit. Lysis product will be used for library preparation with Illumina DNA PCR-Free Prep, Tagmentation library preparation kit and IDT® for Illumina® DNA/RNA Unique Dual Indexes Set A, Tagmentation. Pooled libraries will be sequenced on a NovaSeq 6000. Sequencing data will be automatically transferred to Cloud Space (BaseSpace Sequence Hub) were primary bioinformatic analysis will be performed upon completion of sequencing and data transfer. Annotated variant calling files for SNVs and CNVs will be analyzed with Moon (Invitae) and in-house bioinformatic analysis solutions. Clinical interpretation will be performed by the principal investigator.~WGS results were communicated to pediatrician. The clinical utility survey was filled by clinical geneticists at least a month after the return of sequencing results.
Prospective, multi-site, non-randomized (single arm) study to evaluate the feasibility, the yield and clinical utility of trio WGS in 30 critically ill patients in neonatology intensive care units (NICU) and pediatric intensive care units (PICU) in Belgium. Results are expected to be returned within 7 days after receipt of blood samples in the laboratory. Primary outcome will be evaluated after clinical interpretation, whereas secondary outcome will be evaluated from the clinical utility survey to be completed by clinical geneticists.