LAUSR

Reactivation of fetal haemoglobin (HbF) expression is an effective way to treat β‐thalassaemia and sickle cell anaemia. In the present study, we identified a novel GATA zinc finger domain‐containing protein 2A (GATAD2A) mutation, which contributed to the elevation of HbF and ameliorated clinical severity in a patient with β‐thalassaemia, by targeted next‐generation sequencing. Knockout of GATAD2A led to a significant induction of HbF in both human umbilical cord blood‐derived erythroid progenitor‐2 (HUDEP‐2) and human cluster of differentiation (CD)34+ cells with a detectable impact on erythroid differentiation. Furthermore, heterozygous knockout of GATAD2A impaired recruitment of chromodomain helicase DNA‐binding protein 4 (CHD4) to the methyl‐binding domain protein 2 (MBD2)‐containing nucleosome remodelling and deacetylation (NuRD) complex. Our present data suggest that mutations causing the haploinsufficiency of GATAD2A might contribute to amelioration of clinical severity in patients with β‐thalassaemia.