Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/196815
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, 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.
Subject: Adolescent
Adult
Anemia, Macrocytic
Animals
Blood Platelets
Bone Marrow
Child
Child, Preschool
Erythropoiesis
Female
Gata1 Transcription Factor
Germ-line Mutation
Humans
Infant
Male
Mice
Microscopy, Electron
Pedigree
Protein Isoforms
Rights: fechado
Identifier DOI: 10.1038/ng1825
Address: http://www.ncbi.nlm.nih.gov/pubmed/16783379
Date Issue: 2006
Appears in Collections:Unicamp - Artigos e Outros Documentos

Files in This Item:
File SizeFormat 
pmed_16783379.pdf507.29 kBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.