Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia
Vijay G. Sankaran, … , Eric S. Lander, Hanna T. Gazda
Vijay G. Sankaran, … , Eric S. Lander, Hanna T. Gazda
Published June 18, 2012
Citation Information: J Clin Invest. 2012;122(7):2439-2443. https://doi.org/10.1172/JCI63597.
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Brief Report

Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia

Abstract

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.

Authors

Vijay G. Sankaran, Roxanne Ghazvinian, Ron Do, Prathapan Thiru, Jo-Anne Vergilio, Alan H. Beggs, Colin A. Sieff, Stuart H. Orkin, David G. Nathan, Eric S. Lander, Hanna T. Gazda

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Figure 1

Identification of GATA1 mutations in DBA.

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Identification of GATA1 mutations in DBA. (A) Pedigree of a family wit...
(A) Pedigree of a family with DBA in 2 male children and normal hematological findings in the parents. (B) Sanger sequencing chromatograms from the 3′ end of exon 2 and 5′ end of intron 2 on GATA1 in the mother (I-2) and 3 children from the family shown in A. (C) RT-PCR analysis of GATA1 exons 1 and 3 from peripheral blood RNA samples from the patients (II-1 and II-3); their mother (I-2), who carries the GATA1 mutation; and a normal control. FL, full-length. (D and E) Bone marrow core sections from II-1 and II-3 shown at ×100 magnification demonstrate erythroid hypoplasia. (F) Rare erythroblasts with normal morphology were noted on bone marrow aspirates (from II-1; shown at ×100 magnification). (G) Sanger sequencing chromatograms show a GATA1 G nucleotide deletion (at the exon 2–intron 2 junction) in an independent male patient with DBA.