An inherited mutation leading to production of only the short isoform of GATA-1 is associated with impaired erythropoiesis

dc.creatorHollanda, LM
dc.creatorLima, CSP
dc.creatorCunha, AF
dc.creatorAlbuquerque, DM
dc.creatorVassallo, J
dc.creatorOzelo, MC
dc.creatorJoazeiro, PP
dc.creatorSaad, STO
dc.creatorCosta, FF
dc.date2006
dc.dateJUL
dc.date2014-11-18T20:23:22Z
dc.date2015-11-26T16:58:38Z
dc.date2014-11-18T20:23:22Z
dc.date2015-11-26T16:58:38Z
dc.date.accessioned2018-03-28T23:46:15Z
dc.date.available2018-03-28T23:46:15Z
dc.identifierNature Genetics. Nature Publishing Group, v. 38, n. 7, n. 807, n. 812, 2006.
dc.identifier1061-4036
dc.identifierWOS:000238669300017
dc.identifier10.1038/ng1825
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/54438
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/54438
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/54438
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1277975
dc.descriptionAcquired 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.
dc.description38
dc.description7
dc.description807
dc.description812
dc.languageen
dc.publisherNature Publishing Group
dc.publisherNew York
dc.publisherEUA
dc.relationNature Genetics
dc.relationNature Genet.
dc.rightsfechado
dc.sourceWeb of Science
dc.subjectTransient Myeloproliferative Disorder
dc.subjectAcute Megakaryoblastic Leukemia
dc.subjectTranscription Factor Gata1
dc.subjectX-linked Thrombocytopenia
dc.subjectDown-syndrome
dc.subjectAcquired Mutations
dc.subjectMacrothrombocytopenia
dc.subjectLeukemogenesis
dc.subjectDiagnosis
dc.subjectChildren
dc.titleAn inherited mutation leading to production of only the short isoform of GATA-1 is associated with impaired erythropoiesis
dc.typeArtículos de revistas


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