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- Title
An inherited mutation leading to production of only the short isoform of GATA-1 is associated with impaired erythropoiesis.
- Authors
Hollanda, Luciana M.; Lima, Carmen S. P.; Cunha, Anderson F.; Albuquerque, Dulcinéia M.; Vassallo, José; Ozelo, Margareth C.; Joazeiro, Paulo P.; Saad, Sara T. O.; Costa, Fernando F.
- Abstract
Acquired somatic mutations in exon 2 of the hematopoietic transcription factor GATA-1 have been found in individuals with Down syndrome with both transient myeloproliferative disorder and acute megakaryoblastic leukemia. These mutations prevent the synthesis of the full-length protein but allow the synthesis of its short isoform, GATA-1s. Experiments in mice suggest that GATA-1s supports normal adult megakaryopoiesis, platelet formation and erythropoiesis. Here we report a mutation, 332G → C, in exon 2 of GATA1, leading to the synthesis of only the short isoform in seven affected males from two generations of a family. Hematological profiles of affected males demonstrate macrocytic anemia, normal platelet counts and neutropenia in most cases. Altogether, data suggest that GATA-1s alone, produced in low or normal levels, is not sufficient to support normal erythropoiesis. Moreover, this is the first study to indicate that a germline splicing mutation does not lead to leukemia in the absence of other cooperating events, such as Down syndrome.
- Subjects
ANTIBODY diversity; DOWN syndrome; GENETIC disorders; PROTEIN synthesis; TRANSCRIPTION factors; FAMILIAL diseases; MEDICAL genetics
- Publication
Nature Genetics, 2006, Vol 38, Issue 7, p807
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng1825