Loss of the immunomodulatory transcription factor BATF2 in humans is associated with a neurological phenotype

G Zsurka, MLT Appel, M Nastaly, K Hallmann, N Hansen, D Nass, T Baumgartner, R Surges, G Hartmann, E Bartok, WS Kunz

Research output: Contribution to journalA1: Web of Science-articlepeer-review


Epilepsy and mental retardation are known to be associated with pathogenic mutations in a broad range of genes that are expressed in the brain and have a role in neurodevelopment. Here, we report on a family with three affected individuals whose clinical symptoms closely resemble a neurodevelopmental disorder. Whole-exome sequencing identified a homozygous stop-gain mutation, p.Gln19*, in the BATF2 gene in the patients. The BATF2 transcription factor is predominantly expressed in macrophages and monocytes and has been reported to modulate AP-1 transcription factor-mediated pro-inflammatory responses. Transcriptome analysis showed altered base-level expression of interferon-stimulated genes in the patients’ blood, typical for type I interferonopathies. Peripheral blood mononuclear cells from all three patients demonstrated elevated responses to innate immune stimuli, which could be reproduced in CRISPR–Cas9-generated BATF2−/− human monocytic cell lines. BATF2 is, therefore, a novel disease-associated gene candidate for severe epilepsy and mental retardation related to dysregulation of immune responses, which underscores the relevance of neuroinflammation for epilepsy.
Original languageEnglish
Article number227
Issue number2
Number of pages14
Publication statusPublished - 2023


  • Epilepsy
  • Mental retardation
  • Neuroinflammation
  • Transcription factor
  • Type I interferonopathy


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