title: A Child With Dyserythropoietic Anemia and Megakaryocyte Dysplasia Due to a Novel 5'UTR GATA1s Splice Mutation.
abstract: We describe a child with dyserythropoietic anemia, thrombocytosis, functional platelet defect, and megakaryocyte dysplasia. We show that (i) this constellation of hematopoietic abnormalities was due to a germline mutation within the 5' untranslated region (5'UTR) of globin transcription factor 1 (GATA1); (ii) the mutation impaired a 5'UTR GATA1 splicing site, with promoted production of the shortened GATA1 isoform lacking the N-terminus; and (iii) expression of the GATA1 N-terminus is restricted to erythroblasts and megakaryocytes in normal marrow, consistent with the patient's abnormal erythropoiesis and megakaryopoiesis. Our findings provide insights into the clinically relevant in vivo function of the N-terminal domain of GATA1 in human hematopoiesis.
authors.affiliation: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana.|Division of Pediatric Hematology-Oncology, Bone Marrow Failure Program, Riley Hospital for Children, Indianapolis, Indiana.
authors.forename: Jacob
authors.initials: J
authors.lastname: Zucker
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Constance
authors.initials: C
authors.lastname: Temm
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Czader
authors.affiliation: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana.|Division of Pediatric Hematology-Oncology, Bone Marrow Failure Program, Riley Hospital for Children, Indianapolis, Indiana.|Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana.|Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Nalepa
mesh_terms: D020121:5' Untranslated Regions; D017398:Alternative Splicing; D000742:Anemia, Dyserythropoietic, Congenital / Q000235:genetics* / Q000378:metabolism; D002675:Child, Preschool; D050982:GATA1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008297:Male; D008533:Megakaryocytes; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D022821:RNA Splice Sites
chemical_list: D020121:5' Untranslated Regions; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D020033:Protein Isoforms; D022821:RNA Splice Sites
keywords: GATA1; dyserythropoietic anemia; megakaryocyte dysplasia