Diamond-Blackfan anemia (DBA) is a hypoplastic anemia characterized by impaired 
production of red blood cells, with approximately half of all cases attributed 
to ribosomal protein gene mutations. We performed exome sequencing on two 
siblings who had no known pathogenic mutations for DBA and identified a mutation 
in the gene encoding the hematopoietic transcription factor GATA1. This 
mutation, which occurred at a splice site of the GATA1 gene, impaired production 
of the full-length form of the protein. We further identified an additional 
patient carrying a distinct mutation at the same splice site of the GATA1 gene. 
These findings provide insight into the pathogenesis of DBA, showing that the 
reduction in erythropoiesis associated with the disease can arise from causes 
other than defects in ribosomal protein genes. These results also illustrate the 
multifactorial role of GATA1 in human hematopoiesis.