Professionals

GATAD2A-related Neurodevelopmental Disorder or GARND is caused by mutations in the GATAD2Agene. GARND is an extremely rare multisystem disorder characterized by the variability of its presentation across the few identified patients to date, although affected individuals have typically had global developmental delay and craniofacial dysmorphology.

The GATAD2Agene encodes a protein, GATAD2A (also known as p66-alpha), that is part of the Nucleosome Remodeling and Deacetylase (NuRD) Complex. The NuRD complex is a multiprotein complex that is intrinsically involved in gene regulation, cell-cycle progression, genome integrity, and cellular differentiation.

All NuRD subunits have 2-3 paralogs, which complicates any research of NuRD; however, the GATAD2A-NuRD subtype has been shown to have expression profiles and specific functions that indicate it very important during early embryogenesis.

The extreme rarity of the disorder may be the result of its effects on early embryogenesis and cellular differentiation, leading to increased risk of GATAD2A-variant possessing embryos not being able to complete full development.

To date, there have only been five children identified with GARND. These five children have a range of variant subtypes with variant loci being scattered across the gene. This small sample and genotypic variability has led to a range of GARND phenotypes that can involve the CNS, heart, kidney and other organ systems.

Consistent with its theorized effects on early embryogenesis and variability of variant subtypes, a consistent GARND phenotype has not been identified across the five identified GARND subjects; however, each case has some overlapping phenotypic features with the others. Global developmental delay and craniofacial dysmorphology are the most commonly shared features but are not present in every case.

Some GARND children have some phenotypic overlap with another disorder, GAND, which is associated with GATAD2A’s paralog, GATAD2B. Of note, the GATAD2A and GATAD2B proteins are mutually exclusive paralogs and form two different NuRD subtypes (GATAD2A-NuRD and GATAD2B-NuRD, respectively).