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 de Brevern; Alain Francina; Pierre Ripoche; Odile Fenneteau; Lydie da Costa; Thierry Peyrard; Gail Coghlan; Niels Illum; Henrik Birgens; Hannah Tamary; Achille Iolascon; Jean Delaunay; Gil Tchernia; Jean-Pierre Cartron

doi:10.1016/j.ajhg.2010.10.010

Journal articles

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 ^{7, 6} Alain Francina ⁸ Pierre Ripoche ^{1, 7} Odile Fenneteau ⁹ Lydie da Costa ^{9, 10} Thierry Peyrard ^{1, 11} Gail Coghlan ¹² Niels Illum ¹³ Henrik Birgens ¹⁴ Hannah Tamary ¹⁵ Achille Iolascon ^{16, 17} Jean Delaunay ¹⁸ Gil Tchernia ¹⁰ Jean-Pierre Cartron ¹

* Corresponding author

1 INTS - Institut National de la Transfusion Sanguine [Paris]

2 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy

3 CR Saint-Antoine - Centre de Recherche Saint-Antoine

4 Service de Biochimie [Mondor]

5 Service commun de microscopie électronique

6 DSIMB - Dynamique des Structures et Interactions des Macromolécules Biologiques

7 DSIMB Réunion - Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion

BIGR (UMR_S_1134 / U1134) - Biologie Intégrée du Globule Rouge

8 Unité de Pathologie Moléculaire du Globule Rouge

9 Laboratoire d'Hématologie Biologique

10 Service d'hématologie, immunologie biologiques et cytogénétique

11 CNRGS - Centre National de Référence pour les Groupes Sanguins

12 Department of Pediatrics and Child Health - Department of Pediatrics and Child Health

13 Hans Christian Andersen Children's Hospital - Hans Christian Andersen Children's Hospital

14 Herlev and Gentofte Hospital

15 Pediatric Hematology Unit - Pediatric Hematology Unit

16 Department of Biochemistry and Medical Biotechnologies - Department of Biochemistry and Medical Biotechnologies

17 CEINGE - Biotecnologie Avanzate - CEINGE - Biotecnologie Avanzate

18 Pathologie de la polymérisation des protéines. Substitut du sang et pathologie moléculaire du globule rouge

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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Journal articles

Domain :

Life Sciences [q-bio] / Biochemistry, Molecular Biology

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https://www.hal.inserm.fr/inserm-00550723
Contributor : Alexandre G. de Brevern <>
Submitted on : Wednesday, December 29, 2010 - 6:33:12 PM
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A dominant mutation in the gene encoding the erythroid transcription factor KLF1 causes a congenital dyserythropoietic anemia.

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

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