A dominant mutation in the gene encoding the erythroid transcription factor KLF1 causes a congenital dyserythropoietic anemia.

Lionel Arnaud 1, * Carole Saison 1 Virginie Helias 1 Nicole Lucien 1 Dominique Steschenko 2 Marie-Catherine Giarratana 3 Claude Prehu 4 Bernard Foliguet 5 Lory Montout 1, 6 Alexandre De Brevern 1, 6 Alain Francina 7 Pierre Ripoche 1, 6 Odile Fenneteau 8 Lydie Da Costa 8, 9 Thierry Peyrard 1, 10 Gail Coghlan 11 Niels Illum 12 Henrik Birgens 13 Hannah Tamary 14 Achille Iolascon 15, 16 Jean Delaunay 17 Gil Tchernia 9 Jean-Pierre Cartron 1
Abstract : 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.
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American Journal of Human Genetics, Elsevier (Cell Press), 2010, 87 (5), pp.721-7. 〈10.1016/j.ajhg.2010.10.010〉
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Lionel Arnaud, Carole Saison, Virginie Helias, Nicole Lucien, Dominique Steschenko, et al.. A dominant mutation in the gene encoding the erythroid transcription factor KLF1 causes a congenital dyserythropoietic anemia.. American Journal of Human Genetics, Elsevier (Cell Press), 2010, 87 (5), pp.721-7. 〈10.1016/j.ajhg.2010.10.010〉. 〈inserm-00550723〉

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