Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/54438
Type: Artigo de periódico
Title: An inherited mutation leading to production of only the short isoform of GATA-1 is associated with impaired erythropoiesis
Author: Hollanda, LM
Lima, CSP
Cunha, AF
Albuquerque, DM
Vassallo, J
Ozelo, MC
Joazeiro, PP
Saad, STO
Costa, FF
Abstract: Acquired somatic mutations(1-6) in exon 2 of the hematopoietic transcription factor GATA-1 have been found in individuals with Down syndrome with both transient myeloproliferative disorder(2-10) and acute megakaryoblastic leukemia(1-4,6,8-10). These mutations prevent the synthesis of the full-length protein but allow the synthesis of its short isoform, GATA-1s. Experiments in mice(11) 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.
Country: EUA
Editor: Nature Publishing Group
Rights: fechado
Identifier DOI: 10.1038/ng1825
Date Issue: 2006
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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