Sancho-Shimizu et al. (2011) reported 2 unrelated patients from Saudi Arabia and Europe with HSE resulting from autosomal recessive or autosomal dominant TRIF deficiency. Both patients presented at around 2 years of age with persistent high fever, and ... Sancho-Shimizu et al. (2011) reported 2 unrelated patients from Saudi Arabia and Europe with HSE resulting from autosomal recessive or autosomal dominant TRIF deficiency. Both patients presented at around 2 years of age with persistent high fever, and their cerebrospinal fluid contained herpes simplex virus (HSV)-1. Both patients responded well to different antiviral treatments. Overall, the clinical phenotypes of these 2 patients were remarkably similar to those observed in patients with HSE resulting from UNC93B1 deficiency (610551), TLR3 deficiency (613002), or TRAF3 deficiency (614849).
Sancho-Shimizu et al. (2011) identified causative mutations in the TRIF gene in 2 unrelated patients with HSE. The first patient, a Saudi Arabian boy with autosomal recessive HSE susceptibility, had a homozygous nonsense mutation (R141X; 607601.0001) that resulted ... Sancho-Shimizu et al. (2011) identified causative mutations in the TRIF gene in 2 unrelated patients with HSE. The first patient, a Saudi Arabian boy with autosomal recessive HSE susceptibility, had a homozygous nonsense mutation (R141X; 607601.0001) that resulted in premature termination and no detectable TRIF protein. No other family members were homozygous for this mutation. The second patient, a European girl of mixed European descent with autosomal dominant HSE susceptibility, was heterozygous for a ser186-to-leu (S186L; 607601.0002) substitution in the N terminus of the protein. This patient was the only family member to develop HSE, although her mother and maternal grandfather also carried the S186L mutation and had HSV-1-specific serum antibodies. Sancho-Shimizu et al. (2011) also reported a third patient, an Iranian boy who presented with HSE at age 4.5 years, who was heterozygous for a pro625-to-leu (P625L) missense mutation in the C terminus of TRIF. However, unlike the other TRIF mutations, P625L showed no deleterious effects in cellular assays and was considered nonpathogenic.