Genetic variation in genes of inborn errors of immunity in children with unexplained encephalitis

Area of Science:

• Genetics
• Immunology
• Neurology
• Pediatrics

Background:

• Pediatric encephalitis presents significant morbidity and mortality, with half of cases remaining unexplained.
• The role of host genetics in encephalitis development is recognized but poorly understood.
• Identifying genetic variants is crucial for understanding disease mechanisms and improving diagnostics.

Purpose of the Study:

• To identify rare candidate genetic variants and polymorphisms in children with unexplained encephalitis.
• To investigate the contribution of genetic variations to inborn errors of immunity in pediatric encephalitis.
• To explore potential polygenic risk factors in unexplained pediatric encephalitis cases.

Main Methods:

• Whole genome sequencing was performed on eleven pediatric encephalitis patients (one with anti-NMDA receptor encephalitis, ten unexplained).
• Candidate variants were analyzed using the Human Genetic Mutation Database (Qiagen).
• Variants were categorized into deleterious/potentially deleterious, carrier states, and disease-related polymorphisms.

Main Results:

• 55% of patients had deleterious/potentially deleterious variants in a disease-consistent inheritance pattern.
• 45% were heterozygous carriers for autosomal recessive conditions.
• 55% carried disease-related polymorphisms, and 64% had multiple variants, suggesting polygenic risk.
• Identified variants are implicated in atypical hemolytic uremic syndrome, common variable immunodeficiency, hemophagocytic lymphohistiocytosis, and systemic lupus erythematosus.

Conclusions:

• Preliminary findings indicate genetic variations related to inborn errors of immunity in acute pediatric encephalitis.
• Multiple genetic variants may contribute to polygenic risk in unexplained encephalitis.
• Further research is necessary to establish the functional role of these variants in disease development.