Project Details

Exome sequencing for the discovery of genetic determinants of pediatric anti-NMDAR encephalitis

Alexander Sandweiss, MD, PhD

Summary

BACKGROUND: Anti-NMDAR autoimmune encephalitis (NMDAR AE) is a central nervous system inflammatory disorder that affects children manifesting as seizures, focal weakness, psychosis and cognitive dysfunction with potentially long-term neurocognitive sequelae and lifelong epilepsy. GAP: There are no known non-HLA susceptibility genes specifically associated with anti-NMDAR AE in children. Further, there is a paucity of research focusing on pediatric populations, immune mechanisms, and genetic predispositions in younger, racially and ethnically diverse patient populations. HYPOTHESIS: We hypothesize that children who develop anti-NMDAR AE have a genetic predisposition for monocyte and macrophage dysregulation, and thus a predilection toward autoimmune disorders. METHODS: We will recruit pediatric patients from Texas Children’s Hospital diagnosed with anti-NMDAR AE to obtain genome sequencing that may lead to the discovery of novel gene variants predisposing toward autoimmune encephalitis. RESULTS: Pending. IMPACT: The discovery of disease-associated gene variants will allow the development of specific biomarkers to more rapidly identify the disease. Further, we hope to produce innovative targeted therapies that address the underlying pathophysiology of NMDAR AE.