Case report: Identification of ultra-rare genetic variants in pediatric acute onset neuropsychiatric syndrome (PANS) by exome and whole genome sequencing

“In the current study, we used next generation sequencing to search for ultra-rare genetic variants in patients who met diagnostic criteria for PANS as established by the PANS Consensus Conference.” ²

“Mutations were identified in 21 patients in 11 genes that separate into two broad functional categories: those that affect peripheral innate and adaptive immune pathways, and those that are expressed primarily in cortical neurons, where they function as synaptic regulators and have all been implicated in other neurological and neurodevelopmental disorders.”

“In addition, several genes are expressed in the choroid plexus and brain vasculature, suggesting they might contribute to a breach in the blood-CSF barrier and blood–brain barrier (BBB) that accompanies inflammation and infection.”

“In conclusion, we identified ultra-rare genetic variants in PANS patients that appear to function at multiple levels of the neuroinflammatory circuit, including peripheral and central innate immunity, synaptogenesis, the blood-CSF barrier, and perhaps the enteric nervous system.”