Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Medline ® Abstract for Reference 119

of 'Anemia in children due to decreased red blood cell production'

An inherited mutation leading to production of only the short isoform of GATA-1 is associated with impaired erythropoiesis.
Hollanda LM, Lima CS, Cunha AF, Albuquerque DM, Vassallo J, Ozelo MC, Joazeiro PP, Saad ST, Costa FF
Nat Genet. 2006;38(7):807.
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.
Department of Internal Medicine, Hemocentro, School of Medical Science, Universidade Estadual de Campinas, Campinas, São Paulo 13083-970, Brazil.