A Dominant Mutation in the Gene Encoding the Erythroid Transcription Factor KLF1 Causes a Congenital Dyserythropoietic Anemia

被引：158

作者：

Arnaud, Lionel ^{[1
]}

Saison, Carole ^{[1
]}

Helias, Virginie ^{[1
]}

Lucien, Nicole ^{[1
]}

Steschenko, Dominique ^{[2
]}

Giarratana, Marie-Catherine ^{[3
]}

Prehu, Claude ^{[4
]}

Foliguet, Bernard ^{[5
]}

Montout, Lory ^{[1
,6
,7
]}

de Brevern, Alexandre G. ^{[1
,6
,7
]}

Francina, Alain ^{[8
]}

Ripoche, Pierre ^{[1
,7
]}

Fenneteau, Odile ^{[9
]}

Da Costa, Lydie ^{[9
,10
]}

Peyrard, Thierry ^{[1
,11
]}

Coghlan, Gail ^{[12
]}

Illum, Niels ^{[13
]}

Birgens, Henrik ^{[14
]}

Tamary, Hannah ^{[15
]}

Iolascon, Achille ^{[16
,17
]}

Delaunay, Jean ^{[18
]}

Tchernia, Gil ^{[10
]}

Cartron, Jean-Pierre ^{[1
]}

机构：

[1] Natl Inst Blood Transfus, F-75015 Paris, France

[2] Ctr Hosp Univ Nancy, Hop Enfants Brabois, F-54511 Vandoeuvre Les Nancy, France

[3] Univ Paris 06, UMR S 938, INSERM, Fac Med Pierre & Marie Curie, F-75012 Paris, France

[4] CHU Henri Mondor, Lab Biochim & Genet, F-94010 Creteil, France

[5] Univ Nancy, Serv Commun Microscopie Elect, Fac Med, F-54506 Vandoeuvre Les Nancy, France

[6] Dynam Struct & Interact Macromol Biol, F-75015 Paris, France

[7] Univ Paris 07, UMR S 665, INSERM, Inst Natl Transfus Sanguine, F-75015 Paris, France

[8] Hop Edouard Herriot, Hosp Civils Lyon, Unite Pathol Mol Globule Rouge, F-69003 Lyon, France

[9] Hop Robert Debre, Lab Hematol Biol, Ctr Hosp, F-75019 Paris, France

[10] Hop Bicetre, Hematol Lab, F-94275 Le Kremlin Bicetre, France

[11] Ctr Natl Reference Grp Sanguins, F-75011 Paris, France

[12] Univ Manitoba, Dept Pediat & Child Hlth, Winnipeg, MB R3A 1S1, Canada

[13] Odense Univ Hosp, Hans Christian Andersen Childrens Hosp, DK-5000 Odense, Denmark

[14] Univ Copenhagen, Herlev Hosp, DK-2730 Herlev, Denmark

[15] Schneider Childrens Med Ctr, Pediat Hematol Unit, IL-49202 Petah Tiqwa, Israel

[16] Univ Naples Federico II, Dept Biochem & Med Biotechnol, I-80131 Naples, Italy

[17] Ctr Ingn Genet Biotecnol Avanzate, I-80145 Naples, Italy

[18] Univ Paris 11, UMR S 779, INSERM, Fac Med Paris Sud, F-94275 Le Kremlin Bicetre, France

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2010年 / 87卷 / 05期

基金：

以色列科学基金会;

关键词：

INHERITED MUTATION; BETA-THALASSEMIA; GLOBAL ROLE; BLOOD; EKLF; ERYTHROPOIESIS; PHENOTYPE; CD44; MICE; FORM;

D O I：

10.1016/j.ajhg.2010.10.010

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 unclasified 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

引用

页码：721 / 727

页数：7

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