PUBLICATION
Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type II
- Authors
- Schwarz, K., Iolascon, A., Verissimo, F., Trede, N.S., Horsley, W., Chen, W., Paw, B.H., Hopfner, K.P., Holzmann, K., Russo, R., Esposito, M.R., Spano, D., De Falco, L., Heinrich, K., Joggerst, B., Rojewski, M.T., Perrotta, S., Denecke, J., Pannicke, U., Delaunay, J., Pepperkok, R., and Heimpel, H.
- ID
- ZDB-PUB-090706-6
- Date
- 2009
- Source
- Nature Genetics 41(8): 936-940 (Journal)
- Registered Authors
- Paw, Barry, Trede, Nick
- Keywords
- none
- MeSH Terms
-
- Anemia, Dyserythropoietic, Congenital/genetics*
- Animals
- COP-Coated Vesicles/genetics*
- Cell Line
- Cell Nucleus/genetics
- DNA Mutational Analysis
- Erythroid Cells/metabolism
- Humans
- Jaw/pathology
- Mutation/genetics*
- Phenotype
- Vesicular Transport Proteins/genetics*
- Zebrafish/genetics
- PubMed
- 19561605 Full text @ Nat. Genet.
Citation
Schwarz, K., Iolascon, A., Verissimo, F., Trede, N.S., Horsley, W., Chen, W., Paw, B.H., Hopfner, K.P., Holzmann, K., Russo, R., Esposito, M.R., Spano, D., De Falco, L., Heinrich, K., Joggerst, B., Rojewski, M.T., Perrotta, S., Denecke, J., Pannicke, U., Delaunay, J., Pepperkok, R., and Heimpel, H. (2009) Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type II. Nature Genetics. 41(8):936-940.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping