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 Iolascon & 3 andre Jean Delaunay, Gil Tchernia, Jean-Pierre Cartron

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Human Genetics
Vol/bind87
Udgave nummer5
Sider (fra-til)721-7
ISSN0002-9297
DOI
StatusUdgivet - 2010

Fingeraftryk

Erythropoiesis
Mutation
Globins
Essential Genes
Missense Mutation
Hemolysis

Citer dette

Arnaud, Lionel ; Saison, Carole ; Helias, Virginie ; Lucien, Nicole ; Steschenko, Dominique ; Giarratana, Marie-Catherine ; Prehu, Claude ; Foliguet, Bernard ; Montout, Lory ; de Brevern, Alexandre G ; Francina, Alain ; Ripoche, Pierre ; Fenneteau, Odile ; Da Costa, Lydie ; Peyrard, Thierry ; Coghlan, Gail ; Illum, Niels ; Birgens, Henrik ; Tamary, Hannah ; Iolascon, Achille ; Delaunay, Jean ; Tchernia, Gil ; Cartron, Jean-Pierre. / A dominant mutation in the gene encoding the erythroid transcription factor KLF1 causes a congenital dyserythropoietic anemia. I: American Journal of Human Genetics. 2010 ; Bind 87, Nr. 5. s. 721-7.
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title = "A dominant mutation in the gene encoding the erythroid transcription factor KLF1 causes a congenital dyserythropoietic anemia",
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.",
keywords = "Anemia, Dyserythropoietic, Congenital, Base Sequence, Cell Differentiation, Erythroblasts, Erythropoiesis, Humans, Infant, Newborn, Kruppel-Like Transcription Factors, Male, Models, Molecular, Mutation",
author = "Lionel Arnaud and Carole Saison and Virginie Helias and Nicole Lucien and Dominique Steschenko and Marie-Catherine Giarratana and Claude Prehu and Bernard Foliguet and Lory Montout and {de Brevern}, {Alexandre G} and Alain Francina and Pierre Ripoche and Odile Fenneteau and {Da Costa}, Lydie and Thierry Peyrard and Gail Coghlan and Niels Illum and Henrik Birgens and Hannah Tamary and Achille Iolascon and Jean Delaunay and Gil Tchernia and Jean-Pierre Cartron",
note = "Copyright {\circledC} 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.",
year = "2010",
doi = "10.1016/j.ajhg.2010.10.010",
language = "English",
volume = "87",
pages = "721--7",
journal = "American Journal of Human Genetics",
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Arnaud, L, Saison, C, Helias, V, Lucien, N, Steschenko, D, Giarratana, M-C, Prehu, C, Foliguet, B, Montout, L, de Brevern, AG, Francina, A, Ripoche, P, Fenneteau, O, Da Costa, L, Peyrard, T, Coghlan, G, Illum, N, Birgens, H, Tamary, H, Iolascon, A, Delaunay, J, Tchernia, G & Cartron, J-P 2010, 'A dominant mutation in the gene encoding the erythroid transcription factor KLF1 causes a congenital dyserythropoietic anemia', American Journal of Human Genetics, bind 87, nr. 5, s. 721-7. https://doi.org/10.1016/j.ajhg.2010.10.010

A dominant mutation in the gene encoding the erythroid transcription factor KLF1 causes a congenital dyserythropoietic anemia. / Arnaud, Lionel; Saison, Carole; Helias, Virginie; Lucien, Nicole; Steschenko, Dominique; Giarratana, Marie-Catherine; Prehu, Claude; Foliguet, Bernard; Montout, Lory; de Brevern, Alexandre G; Francina, Alain; Ripoche, Pierre; Fenneteau, Odile; Da Costa, Lydie; Peyrard, Thierry; Coghlan, Gail; Illum, Niels; Birgens, Henrik; Tamary, Hannah; Iolascon, Achille; Delaunay, Jean; Tchernia, Gil; Cartron, Jean-Pierre.

I: American Journal of Human Genetics, Bind 87, Nr. 5, 2010, s. 721-7.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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 - Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

PY - 2010

Y1 - 2010

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.

KW - Anemia, Dyserythropoietic, Congenital

KW - Base Sequence

KW - Cell Differentiation

KW - Erythroblasts

KW - Erythropoiesis

KW - Humans

KW - Infant, Newborn

KW - Kruppel-Like Transcription Factors

KW - Male

KW - Models, Molecular

KW - Mutation

U2 - 10.1016/j.ajhg.2010.10.010

DO - 10.1016/j.ajhg.2010.10.010

M3 - Journal article

VL - 87

SP - 721

EP - 727

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 5

ER -