Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia

J Clin Invest. 2012 Jul;122(7):2439-43. doi: 10.1172/JCI63597. Epub 2012 Jun 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Diamond-Blackfan / genetics*
  • Base Sequence
  • Case-Control Studies
  • DNA Mutational Analysis
  • Exome*
  • GATA1 Transcription Factor / genetics*
  • GATA1 Transcription Factor / metabolism
  • Genetic Association Studies
  • Hematopoiesis
  • Humans
  • Male
  • Real-Time Polymerase Chain Reaction
  • Sequence Deletion
  • Young Adult


  • GATA1 Transcription Factor
  • GATA1 protein, human