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

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

L. Arnaud, C. Saison, V. Helias, N. Lucien, D. Steschenko, M.C. Giarratana, C. Prehu, B. Foliguet, L. Montout, A.G. de Brevern, A. Francina, P. Ripoche, O. Fenneteau, L. Da Costa, T. Peyrard, G. Coghlan, N. Illum, H. Birgens, H. Tamary, A. IolasconJ. Delaunay, G. Tchernia, J.P. Cartron

    162 Citationer (Scopus)

    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 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
    Bidragets oversatte titelA Dominant Mutation in the Gene Encoding the Erythroid Transcription Factor KLF1 Causes a Congenital Dyserythropoietic Anemia
    OriginalsprogEngelsk
    TidsskriftAmerican Journal of Human Genetics
    Vol/bind87
    Udgave nummer5
    Sider (fra-til)721-727
    Antal sider7
    ISSN0002-9297
    StatusUdgivet - 2010

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