Development and Validation of a Targeted Next-Generation Sequencing Gene Panel for Children With Neuroinflammation

Key Points Question Is a customized gene panel associated with identification of monogenic disease-causing mutations in children with unclassified neuroinflammation? Findings This cohort study developed a targeted sequencing approach using a panel of 257 genes, including those involved in neuroinflammation and mimics of neuroinflammation. In a cohort of 60 children with suspected genetic neuroinflammation, a molecular diagnosis was ascertained in 20% of patients, highlighting some unexpected genotype-phenotype associations and novel pathogenic variants. Meaning Use of this gene panel may help obtain an accurate molecular diagnosis in a timely fashion to guide patient management, including early targeted treatment and early institution of allogeneic hematopoietic stem cell transplantation.