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

Lionel Arnaud*, Carole Saison, Virginie Helias, Nicole Lucien, Dominique Steschenko, Marie Catherine Giarratana, Claude Prehu, Bernard Foliguet, Lory Montout, Alexandre G. De Brevern, Alain Francina, Pierre Ripoche, Odile Fenneteau, Lydie Da Costa, Thierry Peyrard, Gail Coghlan, Niels Illum, Henrik Birgens, Hannah Tamary, Achille IolasconJean Delaunay, Gil Tchernia, Jean Pierre Cartron

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

158 Scopus citations


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.

Original languageEnglish
Pages (from-to)721-727
Number of pages7
JournalAmerican Journal of Human Genetics
Issue number5
StatePublished - 12 Nov 2010
Externally publishedYes


FundersFunder number
Israeli Ministry of Science, Culture, and Sport
Israeli Ministry of Science-Eshkol
Italian Ministry of University and ResearchMUR-PS 35-126/Ind
National Institute for Health and Medical Research
Winnipeg Rh Institute Foundation
Institut national de la santé et de la recherche médicale
Fondazione TelethonGGP09044
Regione CampaniaDGRC 1901/2009
Israel Science Foundation699/_03-18.4
Université Paris Diderot
Institut national de la transfusion sanguine


    Dive into the research topics of 'A dominant mutation in the gene encoding the erythroid transcription factor KLF1 causes a congenital dyserythropoietic anemia'. Together they form a unique fingerprint.

    Cite this