Novel Intragenic Duplication of GATAD2B in a Patient With GAND

The nucleosome remodeling and deacetylation (NuRD) complex is a major chromatin regulator and plays a critical role in regulating gene transcription, genome integrity, and cell cycle progression. Heterozygous variants in GATAD2B , a core NuRD component, have been reported to cause GATAD2B ‐Associated Neurodevelopmental Disorder (GAND), an autosomal dominant neurodevelopmental disorder characterized by intellectual disability, developmental delay, hypotonia, and distinctive craniofacial features. The vast majority of disease‐causing variants in GATAD2B reported to date are loss‐of‐function (nonsense, frameshift, or splice site) variants. Here, we report a 6‐year‐old male patient with profound global developmental delay and dysmorphic features, who was found to have a de novo ~97 kbp partial duplication of the GATAD2B gene. Using long‐read transcriptome and genome sequencing on the Pacific BioSciences (PacBio) platform, we show that the duplication is a tandem event whose breakpoint in the 3′ UTR of the gene causes skipping of the last exon and transcriptional read‐through. The resulting transcript contains two incomplete copies of GATAD2B , one with exons 1–10 and the other with exons 2–7, likely representing a loss‐of‐function allele. Follow‐up clinical evaluations confirmed the patient's diagnosis of GAND, ending a years‐long diagnostic odyssey for the family and highlighting an unusual mechanism of gene disruption in GATAD2B .