TY - JOUR
T1 - A dominant mutation in the gene encoding the erythroid transcription factor KLF1 causes a congenital dyserythropoietic anemia
AU - Arnaud, Lionel
AU - Saison, Carole
AU - Helias, Virginie
AU - Lucien, Nicole
AU - Steschenko, Dominique
AU - Giarratana, Marie Catherine
AU - Prehu, Claude
AU - Foliguet, Bernard
AU - Montout, Lory
AU - De Brevern, Alexandre G.
AU - Francina, Alain
AU - Ripoche, Pierre
AU - Fenneteau, Odile
AU - Da Costa, Lydie
AU - Peyrard, Thierry
AU - Coghlan, Gail
AU - Illum, Niels
AU - Birgens, Henrik
AU - Tamary, Hannah
AU - Iolascon, Achille
AU - Delaunay, Jean
AU - Tchernia, Gil
AU - Cartron, Jean Pierre
N1 - Funding Information:
First, we would like to thank the patients and patient ME's relatives for providing blood samples for this study. We would like also to thank D. Sommelet, J. Buisine, L. Douay, M. Goossens, C. Etchebest, Y. Colin, T. Zelinski, P. Gane, T. Cynober, M. Feneant-Thibault, C. Schmitt, R. Russo, M.R. Esposito, C. Menanteau, S. Kappler-Gratias, B.-N. Pham, P.-Y. Le Pennec, E. Vera, C. Verheyde, G. Nicolas, B.A. Ballif, and M. Le Gall for their contributions to this study. L.A. and J.-P.C. were supported by the National Institute of Blood Transfusion (INTS), the National Institute for Health and Medical Research (INSERM), and Paris Diderot University (Paris 7). G.C. was supported by an operating grant from the Winnipeg Rh Institute Foundation to T. Zelinski. H.T. was supported by an Israel Science Foundation grant (No. 699/_03-18.4), by an Israeli Ministry of Science, Culture, and Sport grant in the framework of the Israel-France Program, and by an Israeli Ministry of Science-Eshkol Fellowship. A.I. was supported by the Italian Ministry of University and Research (grant MUR-PS 35-126/Ind), the Italian Telethon Foundation (project GGP09044), and Regione Campania (DGRC 1901/2009).
PY - 2010/11/12
Y1 - 2010/11/12
N2 - The congenital dyserythropoietic anemias (CDAs) are inherited red blood cell disorders whose hallmarks are ineffective erythropoiesis, hemolysis, and morphological abnormalities of erythroblasts in bone marrow. We have identified a missense mutation in KLF1 of patients with a hitherto unclassified CDA. KLF1 is an erythroid transcription factor, and extensive studies in mouse models have shown that it plays a critical role in the expression of globin genes, but also in the expression of a wide spectrum of genes potentially essential for erythropoiesis. The unique features of this CDA confirm the key role of KLF1 during human erythroid differentiation. Furthermore, we show that the mutation has a dominant-negative effect on KLF1 transcriptional activity and unexpectedly abolishes the expression of the water channel AQP1 and the adhesion molecule CD44. Thus, the study of this disease-causing mutation in KLF1 provides further insights into the roles of this transcription factor during erythropoiesis in humans.
AB - The congenital dyserythropoietic anemias (CDAs) are inherited red blood cell disorders whose hallmarks are ineffective erythropoiesis, hemolysis, and morphological abnormalities of erythroblasts in bone marrow. We have identified a missense mutation in KLF1 of patients with a hitherto unclassified CDA. KLF1 is an erythroid transcription factor, and extensive studies in mouse models have shown that it plays a critical role in the expression of globin genes, but also in the expression of a wide spectrum of genes potentially essential for erythropoiesis. The unique features of this CDA confirm the key role of KLF1 during human erythroid differentiation. Furthermore, we show that the mutation has a dominant-negative effect on KLF1 transcriptional activity and unexpectedly abolishes the expression of the water channel AQP1 and the adhesion molecule CD44. Thus, the study of this disease-causing mutation in KLF1 provides further insights into the roles of this transcription factor during erythropoiesis in humans.
UR - http://www.scopus.com/inward/record.url?scp=78249264453&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2010.10.010
DO - 10.1016/j.ajhg.2010.10.010
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C2 - 21055716
AN - SCOPUS:78249264453
SN - 0002-9297
VL - 87
SP - 721
EP - 727
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 5
ER -