title: Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type II.
abstract: Congenital dyserythropoietic anemias (CDAs) are phenotypically and genotypically heterogeneous diseases. CDA type II (CDAII) is the most frequent CDA. It is characterized by ineffective erythropoiesis and by the presence of bi- and multinucleated erythroblasts in bone marrow, with nuclei of equal size and DNA content, suggesting a cytokinesis disturbance. Other features of the peripheral red blood cells are protein and lipid dysglycosylation and endoplasmic reticulum double-membrane remnants. Development of other hematopoietic lineages is normal. Individuals with CDAII show progressive splenomegaly, gallstones and iron overload potentially with liver cirrhosis or cardiac failure. Here we show that the gene encoding the secretory COPII component SEC23B is mutated in CDAII. Short hairpin RNA (shRNA)-mediated suppression of SEC23B expression recapitulates the cytokinesis defect. Knockdown of zebrafish sec23b also leads to aberrant erythrocyte development. Our results provide in vivo evidence for SEC23B selectivity in erythroid differentiation and show that SEC23A and SEC23B, although highly related paralogous secretory COPII components, are nonredundant in erythrocyte maturation.
authors: Institute for Transfusion Medicine, University of Ulm, Ulm, Germany. klaus.schwarz@uni-ulm.de
authors: Klaus
authors: K
authors: Schwarz
authors: Achille
authors: A
authors: Iolascon
authors: Fatima
authors: F
authors: Verissimo
authors: Nikolaus S
authors: NS
authors: Trede
authors: Wyatt
authors: W
authors: Horsley
authors: Wen
authors: W
authors: Chen
authors: Barry H
authors: BH
authors: Paw
authors: Karl-Peter
authors: KP
authors: Hopfner
authors: Karlheinz
authors: K
authors: Holzmann
authors: Roberta
authors: R
authors: Russo
authors: Maria Rosaria
authors: MR
authors: Esposito
authors: Daniela
authors: D
authors: Spano
authors: Luigia
authors: L
authors: De Falco
authors: Katja
authors: K
authors: Heinrich
authors: Brigitte
authors: B
authors: Joggerst
authors: Markus T
authors: MT
authors: Rojewski
authors: Silverio
authors: S
authors: Perrotta
authors: Jonas
authors: J
authors: Denecke
authors: Ulrich
authors: U
authors: Pannicke
authors: Jean
authors: J
authors: Delaunay
authors: Rainer
authors: R
authors: Pepperkok
authors: Hermann
authors: H
authors: Heimpel
mesh_terms: D000742:Anemia, Dyserythropoietic, Congenital / Q000235:genetics*; D000818:Animals; D022181:COP-Coated Vesicles / Q000235:genetics*; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics; D004252:DNA Mutational Analysis; D041905:Erythroid Cells / Q000378:metabolism; D006801:Humans; D007568:Jaw / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D033921:Vesicular Transport Proteins / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics
chemical_list: C543353:SEC23B protein, human; D033921:Vesicular Transport Proteins