In JAMA Network Open, researchers from Columbia University, Regeneron Pharmaceuticals, the New York City Office of Chief Medical Examiner's molecular genetics lab, and New York Presbyterian Hospital uncover excess rare, loss-of-function variants in children with critical illnesses or related deaths. Using exome sequence data for 267 pediatric critical illness cases, 18 deceased children with a history of bronchiolitis, and 9,990 unaffected controls, the team saw enhanced rare or ultrarare loss-of-function variation in 231 of the cases, although most patients were not diagnosed with a genetic condition. "This genetic association study found that critically ill children harbored excess [loss-of-function] variants," the authors reported, concluding that their findings so far "indicate that critically ill children harbor ultrarare risk variants detected by [exome sequencing], even in the absence of genetic diagnoses."