A Child With Dyserythropoietic Anemia and Megakaryocyte Dysplasia Due to a Novel 5′UTR GATA1s Splice Mutation

Jacob Zucker, Constance Temm, Magdalena Czader, Grzegorz Nalepa

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)917-921
Number of pages5
JournalPediatric Blood and Cancer
Volume63
Issue number5
DOIs
StatePublished - May 1 2016

Fingerprint

Megakaryocytes
5' Untranslated Regions
Anemia
GATA1 Transcription Factor
Thrombocytosis
Erythroblasts
Mutation
Germ-Line Mutation
Erythropoiesis
Hematopoiesis
Protein Isoforms
Blood Platelets
Bone Marrow

Keywords

  • Dyserythropoietic anemia
  • GATA1
  • Megakaryocyte dysplasia

ASJC Scopus subject areas

  • Oncology
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

A Child With Dyserythropoietic Anemia and Megakaryocyte Dysplasia Due to a Novel 5′UTR GATA1s Splice Mutation. / Zucker, Jacob; Temm, Constance; Czader, Magdalena; Nalepa, Grzegorz.

In: Pediatric Blood and Cancer, Vol. 63, No. 5, 01.05.2016, p. 917-921.

Research output: Contribution to journalArticle

@article{81af5ce9014e440cbb613751e4e3ad60,
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.",
keywords = "Dyserythropoietic anemia, GATA1, Megakaryocyte dysplasia",
author = "Jacob Zucker and Constance Temm and Magdalena Czader and Grzegorz Nalepa",
year = "2016",
month = "5",
day = "1",
doi = "10.1002/pbc.25871",
language = "English (US)",
volume = "63",
pages = "917--921",
journal = "Pediatric Blood and Cancer",
issn = "1545-5009",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - A Child With Dyserythropoietic Anemia and Megakaryocyte Dysplasia Due to a Novel 5′UTR GATA1s Splice Mutation

AU - Zucker, Jacob

AU - Temm, Constance

AU - Czader, Magdalena

AU - Nalepa, Grzegorz

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

KW - Dyserythropoietic anemia

KW - GATA1

KW - Megakaryocyte dysplasia

UR - http://www.scopus.com/inward/record.url?scp=84961219365&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961219365&partnerID=8YFLogxK

U2 - 10.1002/pbc.25871

DO - 10.1002/pbc.25871

M3 - Article

VL - 63

SP - 917

EP - 921

JO - Pediatric Blood and Cancer

JF - Pediatric Blood and Cancer

SN - 1545-5009

IS - 5

ER -