Characterization of the <Emphasis Type="Italic">N</Emphasis>-glycosylation phenotype of erythrocyte membrane proteins in congenital dyserythropoietic anemia type II (CDA II/HEMPAS) |
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Authors: | Jonas Denecke Christian Kranz Manfred Nimtz Harald S Conradt Thomas Brune Hermann Heimpel Thorsten Marquardt |
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Institution: | (1) Department of Pediatrics, University Hospital of Münster, Albert-Schweitzer-Str. 33, 48149 Munster, Germany;(2) Department of Hematology and Oncology, University Hospital of Ulm, Ulm, Germany;(3) German Research Center for Biotechnology (GBF), GlycoThera inc, Braunschweig, Germany;(4) Department of Pediatrics, University Hospital of Magdeburg, Magdeburg, Germany |
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Abstract: | Congenital dyserythropoetic anemia type II (CDA II) is characterized by bi- and multinucleated erythroblasts and an impaired
N-glycosylation of erythrocyte membrane proteins. Several enzyme defects have been proposed to cause CDA II based on the investigation
of erythrocyte membrane glycans pinpointing to defects of early Golgi processing steps. Hitherto no molecular defect could
be elucidated. In the present study, N-glycosylation of erythrocyte membrane proteins of CDA II patients and controls was investigated by SDS-Page, lectin binding
studies, and MALDI-TOF/MS mapping in order to allow an embracing view on the glycosylation defect in CDA II. Decreased binding
of tomato lectin was a consistent finding in all typical CDA II patients. New insights into tomato lectin binding properties
were found indicating that branched polylactosamines are the main target. The binding of Aleuria aurantia, a lectin preferentially binding to α1-6 core-fucose, was reduced in western blots of CDA II erythrocyte membranes. MALDI-TOF
analysis of band 3 derived N-glycans revealed a broad spectrum of truncated structures showing the presence of high mannose and hybrid glycans and mainly
a strong decrease of large N-glycans suggesting impairment of cis, medial and trans Golgi processing. Conclusion: Truncation of N-glycans is a consistent finding in CDA II erythrocytes indicating the diagnostic value of tomato-lectin studies. However,
structural data of erythrocyte N-glycans implicate that CDA II is not a distinct glycosylation disorder but caused by a defect disturbing Golgi processing
in erythroblasts. |
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Keywords: | Hempas CDA II Congenital disorders of glycosylation Dyserythropoesis Erythrocyte membrane glycosylation |
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