Families

GATAD2A-related Neurodevelopmental Disorder or GARND is caused by mutations in the GATAD2Agene. GARND is an extremely rare disorder affected multiple organ systems 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 regulating gene expression, cell growth and cellular differentiation.

All NuRD subunits have 2-3 paralogs (“related” proteins that are very similar but slightly different), 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 embryonic development.

The extreme rarity of the disorder may be the result of its effects on early embryogenesis and cellular differentiation, leading to increased risk of embryos possessing a GATAD2A-variant being unable 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 variability of mutations has led to a range of GARND presentations that can involve either the CNS, heart, kidney and other organ systems.

Consistent with its theorized effects on early embryogenesis and variability of variant subtypes, a consistent presentation of GARND has not been identified across the five identified subjects; however, each case has some overlapping clinical features with the others.

Global developmental delay and a distinct facial patterning are the most commonly shared features but are not present in every case. Some GARND children have some clinical overlap with another disorder, GAND, which is associated with protein (GATAD2B) that is related to GATAD2A. Of note, the GATAD2A and GATAD2B proteins cannot be present in the same NuRD complex, but make separate NuRD subtypes (GATAD2A-NuRD and GATAD2B-NuRD, respectively).

Currently, the Pierson laboratory have a number of ongoing clinical and basic research studies focused on GATAD2Aand GARND and other NuRD-related disorders (including GAND, the NuRDopathy associated with the GATAD2Bgene).

Please contact Dr. Tyler Mark Pierson at tyler.pierson@cshs.org for criteria and more information about the study.