The GATAD2B gene encodes the GATAD2B protein, which is a part of the NuRD complex. One basic role the GATAD2B protein has is to connect two separate parts of the NuRD complex with each other to make the complex work. Disruption of this bridging role likely disrupts NuRD function and activity, which leads to GAND. Because of this tethering role being a “keystone” required for NuRD function and GATAD2B being expressed during neurodevelopment, children with GAND possesses many of the combined features of most of the other NuRD-related disorders (CHD3-, CHD4-, and CHD5-related disorders) and can be thought of as a “pan-NuRDopathy” with regards to neurodevelopment (this is likely not the case with heart development).
Almost all GAND variants have been identified as de novo, or a new mutation spontaneously generated in the sperm or egg or early embryo.
GAND seems to be the result of a “half-dose” of the GATAD2B protein as we have shown in the GAND mouse and in unpublished data using GAND patient-derived cells.
Some types of GAND variants are located at specific locations on the GATAD2B protein and disrupt the GATAD2B protein’s ability to link up with other proteins in the NuRD complex.
GATAD2B protein and NuRD were previously shown to play a big role in organizing the complex “choreography” that is involved with setting up the micro-architecture of the human cerebral cortex. Decreased NuRD activity has been shown to disrupt the micro-architecture of the brain and lead to it being “mis-wired.”
Diagnostic testing when there is a suspicion of GAND can include intellectual disability gene panels, exome sequencing, and whole genome sequencing.
There is a genetic deletion syndrome involving several genes including GATAD2B being deleted on chromosome 1q21.3. This loss of additional proteins along with GATAD2B causes a GAND+ presentation that may be more severe than the typical GAND presentation.
These deletions can be identified through chromosomal microarray analysis.
GATAD2B