Loss of GATA-1 full length as a cause of Diamond-Blackfan anemia phenotype

Abstract

Mutations in the hematopoietic transcription factor GATA-1 alter the proliferation/differentiation of hemopoietic progenitors. Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. These mutations have been found in patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins. We sequenced GATA-1 in 23 patients that were negative for mutations in the most frequently mutated DBA genes. One patient showed a c.2T > C mutation in the initiation codon leading to the loss of the full-length GATA-1 isoform.

Keywords: Diamond-Blackfan; Gata-1; anemia; erythropoiesis; ribosomal protein.

Fig. 1

GATA-1 mutation; (A) Schematic representation of GATA-1 protein production, Description of normal and alternative translation initiation sites located at methionine 1 and 84, respectively. The GATA-1 mutation in the first ATG in exon 2 promotes the production of only GATA-1 short isoform while in normal condition both isoforms are produced; (B) Sanger sequencing. The mutation c.2T > C is highlighted in the box.