GATAD2B-related intellectual disability due to parental mosaicism and review of literature

摘要

GATA zinc finger domain-containing 2B (GATAD2B) encodes p66beta, a subunit of transcription repressor complex methyl-CpG-binding protein-1 histone deacetylase complex/nucleosome remodelling and deacetylase, and mediates gene silencing. Pathogenic variants in GATAD2B are known to cause mental retardation, autosomal dominant 18, characterized by intellectual disability, limited speech development, generalized hypotonia and dysmorphism. Till date, 17 cases of GATAD2B-related intellectual disability, resulting either from loss-of-function variants in GATAD2B or microdeletions spanning GATAD2B, have been reported. Singleton exome sequencing was performed for index patient. The pathogenic variant identified was validated and segregation analysis was performed by Sanger sequencing. In this study, we report on an additional subject with GATAD2B-related intellectual disability identified through whole exome sequencing. The clinically unaffected father harboured the pathogenic variant in a mosaic state. We review the existing phenotypic and genotypic information for the individuals with this condition. GATAD2B-related intellectual disability is a rare condition with subtle yet recognizable clinical features. In this article, we highlight a consistent clinical profile of subjects with GATAD2B-related intellectual disability.