Premium
A Child With Dyserythropoietic Anemia and Megakaryocyte Dysplasia Due to a Novel 5′UTR GATA1s Splice Mutation
Author(s) -
Zucker Jacob,
Temm Constance,
Czader Magdalena,
Nalepa Grzegorz
Publication year - 2016
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.25871
Subject(s) - gata1 , thrombocytosis , erythropoiesis , haploinsufficiency , haematopoiesis , cancer research , medicine , megakaryocyte , exon , gata2 , diamond–blackfan anemia , transcription factor , alternative splicing , germline mutation , mutation , genetics , biology , anemia , gene , platelet , stem cell , phenotype , rna , ribosome
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.