Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: Epilepsy and mental retardation are known to be associated with pathogenic mutations of a broad range of genes that are expressed in the brain and play a role in neurodevelopment. Here, we report a family with three affected individuals whose clinical symptoms closely resemble a neurodevelopmental disorder. Whole-exome sequencing identified a homozygous stop-gain mutation p.Q19* 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 an 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 for severe epilepsy and mental retardation, related to dysregulation of immune responses, which underscores the relevance of neuroinflammation for epilepsy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE220916 | GEO | 2023/01/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Homo sapiens

Project description:Mental Retardation Patients

| PRJNA120323 | ENA

Genome-wide identification of BATF2 binding sites in HeLa-BATF2 cells

Project description:Basic leucine zipper transcription factors (BATFs) play profound roles in the regulatory networks of gene expression in tumor cells. BATF2, also known as SARI (suppressor of AP-1, regulated by interferon), was able to suppress both growth and migration of various cancers. In searching for BATF2/SARI-specific regulatory DNA elements, we first established a stable BATF2 over-expression HeLa cell line, then employed ChIP-Sequencing in order to identify the responsive DNA motifs for BATF2/SARI.

2015-03-26 | GSE67258 | GEO

Genotyping data from one patient with unexplained mental retardation and a deletion in 15q13

2011-03-05 | GSE20564 | GEO

Recurrent 15q13 microdeletions

Project description:We report a recurrent microdeletion syndrome causing mental retardation, epilepsy and variable facial and digital dysmorphisms. We describe nine patients, including six probands; two with de novo deletions, two who inherited the deletion from an affected parent, and two with unknown inheritance. The proximal breakpoint of the largest deletion is contiguous with breakpoint 3 (BP3) of the Prader-Willi/Angelman region extending 3.95 Mb distally to BP5. A smaller 1.5 Mb deletion has proximal breakpoint within the larger deletion (BP4) and shares the same distal BP5. This recurrent 1.5 Mb deletion contains six genes, including a candidate gene for epilepsy (CHRNA7) that is likely responsible for the observed seizure phenotype. The BP4-BP5 region undergoes frequent inversion, suggesting a possible link between this inversion polymorphism and recurrent deletion. The frequency of these microdeletions in mental retardation cases is ~0.3% (6/2082 tested), a prevalence comparable to that of the Williams, Angelman, and Prader-Willi syndromes. Keywords: microdeletion, genomic disorder, mental retardation, epilepsy Patients were intially screened by BAC array CGH (n=290) or qPCR (n=1040). Patients with potential 15q13 deletions were then analyzed on a custom oligonucleotide array targeted to the 15q13 region, results of which are shown here.

2010-05-26 | E-GEOD-10189 | biostudies-arrayexpress

Recurrent 15q13 microdeletions

2008-02-17 | GSE10189 | GEO

Genotyping data from one patient with unexplained mental retardation and a deletion in 15q13

Project description:Recurrent deletions on 15q13.3 have been identified as a predisposition to mental retardation, epilepsy and psychiatric disease. We report compound heterozygous deletions on 15q13.3 in one patients with severe encephalopathy and seizures. We analysed two independent patients with severe encephalopathy and seizures and found heterozygous deletions on 15q13.3 in both patients.

2011-03-05 | E-GEOD-20564 | biostudies-arrayexpress

Effect of Batf2 deficiency on gene epxression in murine alveolar macrophages treated ex vivo with IFNg and K. pneumoniae supernatant

Project description:Basic leucine zipper transcription factor ATF-like 2 (BATF2) is a transcription factor that is emerging as an important regulator of the innate immune system. We previously identified BATF2 among the top upregulated genes in human alveolar macrophages treated with LPS, but the signaling pathways that induce BATF2 expression in response to Gram-negative stimuli are incompletely understood. In addition, the role of BATF2 in the host response to pulmonary infection with a Gram-negative pathogen like Klebsiella pneumoniae (Kp) is not known. We show that induction of Batf2 gene expression in macrophages in response to Kp in vitro requires TRIF and type I interferon (IFN) signaling, but not MyD88 signaling. Analysis of the impact of BATF2-deficiency on macrophage effector functions in vitro showed that BATF2 does not directly impact macrophage phagocytic uptake and intracellular killing of Kp. However, BATF2 markedly enhanced macrophage pro-inflammatory gene expression and Kp-induced cytokine responses. In vivo, we observed that Batf2 gene expression was elevated in the lung tissue of wild type (WT) mice 24 h after pulmonary Kp infection, and Kp-infected BATF2-deficient (Batf2-/-) mice displayed a modest but significant increase in bacterial burden in the lung, spleen and liver compared to WT mice. WT and Batf2-/- mice showed similar recruitment of leukocytes following infection, but in line with our in vitro observations, pro-inflammatory cytokine levels in the alveolar space were reduced in Batf2-/- mice. Altogether, these results suggest that BATF2 enhances pro-inflammatory cytokine responses in macrophages in response to Kp, and that as such, BATF2 contributes to the host defense against pulmonary Kp infection.

2023-08-31 | GSE235114 | GEO

A comprehensive analysis of gene expression patterns in wild-type and Batf2-/- bone marrow-derived macrophages (BMMφ)

Project description:We previously identified TLR-independent expression of 4933430F08Rik, encoding Batf2, in T. cruzi-infected bone marrow-derived dendritic cells (BMDCs) (Kayama et al., 2009). To determine the functions of Batf2 in innate immune responses, we performed a comprehensive gene expression analysis in wild-type and Batf2-/- bone marrow-derived macrophages (BMMφ). RNA-seq analysis showed that 98 genes are upregulated in Batf2-/- BMMφ stimulated with LPS following IFN-γ treatment, when compared with that in wild-type cells. Among these genes, we focused on Il23a, encoding IL-23p19, because IL-23 is able to promote expression of Il17a in Th17 cells.

2017-03-27 | GSE81724 | GEO

Mental Retardation Patients

Project description:Profiling the genomic profiles of mental retardation patients. 13 mental retardation patients were selected for detection of genomic aberrations.

2009-12-16 | GSE19457 | GEO

Project description:ARX transcription factor implicated in mental retardation and epilepsy

| PRJNA143941 | ENA