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Title: Incomplete synthesis of N-glycans in congenital dyserythropoietic anemia type II caused by a defect in the gene encoding. alpha. -mannosidase II

Congenital dyserythropoietic anemia type II, or hereditary erythroblastic multinuclearity with a positive acidified-serum-lysis test (HEMPAS), is a genetic anemia in humans inherited by an autosomally recessive mode. The enzyme defect in most HEMPAS patients has previously been proposed as a lowered activity of N-acetylglucosaminyltransferase II, resulting in a lack of polylactosamine on proteins and leading to the accumulation of polylactosaminyl lipids. A recent HEMPAS case, G.C., has now been analyzed by cell-surface labeling, fast-atom-bombardment mass spectrometry of glycopeptides, and activity assay of glycosylation enzymes. Significantly decreased glycosylation of polylactosaminoglycan proteins and incompletely processed asparagine-linked oligosaccharides were detected in the erythrocyte membranes of G.C. These results suggest that G.C. cells contain a mutation in {alpha}-ManII-encoding gene that results in inefficient expression of {alpha}-ManII mRNA, either through reduced transcription or message instability. This report demonstrates that HEMPAS is caused by a defective gene encoding an enzyme necessary for the synthesis of asparagine-linked oligosaccharides.
Authors:
;  [1] ;  [2] ;  [3] ;  [4]
  1. (La Jolla Cancer Research Foundation, CA (USA))
  2. (Imperial College of Science Technology and Medicine, London (England))
  3. (Hammersmith Hospital, London (England))
  4. (Massachusetts Institute of Technology, Cambridge, MA (USA))
Publication Date:
OSTI Identifier:
5685258
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA); Journal Volume: 87:19
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; GLYCOPROTEINS; MASS SPECTRA; GLYCOSYL TRANSFERASES; GENE MUTATIONS; OLIGOSACCHARIDES; BIOSYNTHESIS; ANEMIAS; CONGENITAL DISEASES; GLYCOLIPIDS; HEREDITARY DISEASES; METABOLIC DISEASES; PATIENTS; RECESSIVE MUTATIONS; RECOMBINANT DNA; CARBOHYDRATES; DISEASES; DNA; ENZYMES; HEMIC DISEASES; LIPIDS; MUTATIONS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; PROTEINS; SACCHARIDES; SPECTRA; SYMPTOMS; SYNTHESIS; TRANSFERASES 550201* -- Biochemistry-- Tracer Techniques