Novel GATAD2B loss-of-function mutations cause intellectual disability in two unrelated cases

• DOI: 10.1038/jhg.2016.164
• Publication Date: 2017-01-12T07:20:51Z
• Authors: Xiaomei Luo; Yongyi Zou; Bo Tan; Yue Zhang; Jing Guo; Lanlan Zeng; Rui Zhang; Hu Tan; Xianda Wei; Yiqiao Hu; Yu Zheng; Desheng Liang; Lingqian Wu
• Keywords: Male; 0301 basic medicine; Heterozygote; High-Throughput Nucleotide Sequencing; GATA Transcription Factors; Repressor Proteins; 03 medical and health sciences; Child, Preschool; Intellectual Disability; Humans; Female; Child; Frameshift Mutation; Genetic Association Studies

GATA zinc finger domain-containing 2B (GATAD2B) is a subunit of the methyl-CpG-binding protein-1 complex (MECP1), which deacetylates methylated nucleosomes and regresses transcriptional activity. Recently, GATAD2B has been elucidated as a candidate gene in patients with intellectual disability (ID). In this study, we identified two novel heterozygous frameshift mutations of GATAD2B in two unrelated ID cases through next-generation sequencing (NGS). Both of the mutations c.80_81insGATGT and c.552_555delGAAA cause truncated proteins that might be detrimental to neurodevelopment. We performed western blotting and observed a reduction in the target protein compared with normal controls. This is the first report of GATAD2B in Chinese ID patients. Our findings will broaden the spectrum of GATAD2B mutations and facilitate genetic diagnosis and counseling.