A potential novel genetic etiology of autoimmune encephalopathy

Background: Encephalitis refers to inflammation of the brain parenchyma, which frequently leads to significant morbidity and mortality. A specific cause is identified in only half of the cases, with viral and autoimmune origins being the most common. In the remaining cases, the cause of encephalitis often remains unknown. Rare genetic conditions manifesting as encephalitis have been identified. Interferon regulatory factor 3 (IRF3) is a key transcription regulator involved in cellular responses, playing an essential role in innate immunity. However, IRF3 may also contribute to harmful immune responses, such as those seen in proinflammatory and autoimmune diseases. Several genetic variants or single nucleotide polymorphisms within IRF genes have been found at higher frequencies in patients with autoimmune diseases compared to healthy controls, suggesting a link to either increased risk or protection against these diseases.

Methods: Our patient’s medical record was analyzed retrospectively, including his medical history, as well as results from immune laboratory tests and genetic analyses.

Results: We present a 19-year-old male with autoimmune encephalopathy. Whole exome sequencing analysis revealed a novel heterozygous variant in the IRF3 gene (NM_001571.6), c.910G>A resulting in p.Gly304Arg.

Conclusion: The presence of IRF3 mutations may lead to the development of autoimmune encephalopathy.

Statement of Novelty: We have identified a novel variant in the IRF3 gene in a patient with autoimmune encephalopathy.