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

Journal Article · Mon Oct 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.19.7443· OSTI ID:5685258

Fukuda, M N; Masri, K A ^[1]; Dell, A ^[2]; Luzzatto, L ^[3]; Moremen, K W ^[4]

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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)

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.

• OSTI ID: 5685258
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 87:19; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

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