A de novo in-frame deletion variant in the BRD4 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2012; functional characterization in Korb et al., 2017 demonstrated that this variant prevented a Brd4-induced increase in spine formation in transfected neurons compared to wild-type Brd4, suggesting a loss-of-function effect. Korb et al., 2017 also demonstrated that Brd4 was upregulated in a mouse model of Fragile X syndrome (FXS), and that inhibition of Brd4 function by the inhibitor JQ1 alleviated many of the phenotypes associated with Fragile X syndrome that were observed in FXS mice. De novo missense variants in BRD4 have also been identified in ASD probands from the Simons Simplex Collection (Krumm et al., 2015). Jouret et al., 2022 reported 14 individuals with either point mutations or deletions affecting the BRD4 gene and found that microcephaly, initial global developmental delay, intellectual disability/learning disability, psychiatric disorders, and dysmorphic features were frequently observed phenotypes.
Molecular Function
BRD4 encodes a chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation. The protein encoded by the BRD4 gene remains associated with acetylated chromatin throughout the entire cell cycle and provides epigenetic memory for postmitotic G1 gene transcription by preserving acetylated chromatin status and maintaining high-order chromatin structure.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
De novo gene disruptions in children on the autistic spectrum.
