Rare Genetic Variants in Immune Genes and Neonatal Herpes Simplex Viral Infections

Neonatal herpes simplex virus (HSV) infection is a devastating disease with high mortality, particularly when disseminated. Studies in adults and children suggest that susceptibility to encephalitis (HSE) may represent phenotypes for inborn errors toll-like receptor 3 (TLR3) signaling. However, the genetic basis of neonatal HSV including disseminated remains unknown. To test hypothesis variants known HSE-susceptible genes as well mediating immunity will be identified HSV, we performed an unbiased exome sequencing study 10 newborns disseminated, HSE, skin, eyes, mouth disease. Determination potential impact on function was determined by following American College Medical Genetics Genomics guidelines. We deleterious potentially deleterious, rare HSE-related stop IRF3 variant (disseminated), nonsynonymous TLR3 TRAF3 (HSE), STAT1 (skin, mouth), DBR1 (disseminated) our cohort. Novel other immunodeficiency or HSV-related immune GRB2, RAG2, PRF1, C6, C7, MSR1 were found 4 infants. The essential T-lymphocyte cell responses novel not public databases. In this pilot study, pathway regulate anti-HSV neonates Larger, definitive studies incorporating functional analysis are required validate these data determine role susceptibility.