Disease relevance of CDAN2

• Three main types of CDA have been distinguished: CDA I and CDA III, whose loci have been already mapped, and CDA II (MIM 224100), the most frequent among CDAs, which is transmitted as an autosomal recessive trait and is known also as "HEMPAS" (hereditary erythroblast multinuclearity with positive acidified serum) [1].
• The hematologic study showed an atypical CDA (hydrops fetalis-associated CDA) characterized by features resembling CDA type II, but negative acidified serum lysis test (HEMPAS negative) [2].
• Susceptibility to hemolysis in acidified serum is a pathognomonic feature of hereditary erythroblastic multinuclearity with a positive acidified serum lysis test (HEMPAS, congenital dyserythropoietic anemia type II) [3].
• Abnormal glycosylation of serum glycoproteins and association of liver cirrhosis in HEMPAS patients indicate that HEMPAS disease is not restricted to erythroid cells [4].
• Polylactosamines are not obligate receptors for invasion of Plasmodium falciparum malaria as shown in HEMPAS variant II-gal- erythrocytes [5].

High impact information on CDAN2

• After the exclusion of three candidate genes, we ob-tained conclusive evidence for linkage of CDA II to microsatellite markers on the long arm of chromosome 20 (20q11.2) [1].
• 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 [6].
• 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 [6].
• This report demonstrates that HEMPAS is caused by a defective gene encoding an enzyme necessary for the synthesis of asparagine-linked oligosaccharides [6].
• From a practical point of view, screening the above minor proteins in RBC membranes appears to be a straightforward and reliable diagnostic test for CDAII [7].

Chemical compound and disease context of CDAN2

• Accumulation of glycolipids containing N-acetylglucosamine in erythrocyte stroma of patients with congenital dyserythropoietic anemia type II (HEMPAS) [8].
• Carbohydrate-deficient glycoprotein syndrome type II. An autosomal recessive N-acetylglucosaminyltransferase II deficiency different from typical hereditary erythroblastic multinuclearity, with a positive acidified-serum lysis test (HEMPAS) [9].
• AIM: To illustrate the possible role of cell differential agent-II (CDA-II) in the apoptosis of hepatoma cells induced by arsenic trioxide (As(2)O(3)) [10].

Biological context of CDAN2

• Neither deficiency of CD44 nor absence of Colton antigens are general features of CDA because erythrocytes from patients with CDA I, CDA II, CDA III, and two other unclassified CDAs had normal expression of CD44 and normal Colton blood group phenotypes [11].
• The parasite was found to invade HEMPAS Variant II-gal- erythrocytes at a 30% lower rate through two life cycles, as shown by microscopic evaluation of invasion and by [3H]hypoxanthine incorporation into parasite [5].
• 2. In CDA II and, to a lesser extent, in CDA I, the in vitro endogenous phosphorylation of band 2 + 2.1 was sharply reduced [12].
• Unexpectedly, she had the same microsatellite assortments around the CDAN2 alleles as her three sisters with CDA II [13].
• Suppression of CDA II expression in a homozygote [13].

Anatomical context of CDAN2

• The aim of the present study was to investigate a possibility that heterozygosity with respect to CDAN2 gene in healthy carriers could be detected by analysis of erythrocyte membrane glycoconjugates [14].
• These observations suggest that band 3s cluster before they are incorporated into the plasma membranes of HEMPAS erythrocytes [15].
• The results strongly suggest that biosynthesis of Asn-linked oligosaccharide chains in HEMPAS hepatocytes is disturbed [16].
• Based on studies of cultures of BFU-E, similar conclusions were previously made for CDA II [17].
• Congenital dyserythropoietic anaemia type II (HEMPAS): characterization of aberrant intracellular organelles by immunogold electron microscopy [18].

Associations of CDAN2 with chemical compounds

• Fast-atom bombardment mass spectrometry analysis of G.K.'s erythrocyte glycopeptides detected a series of high mannose-type oligosaccharides, which were not detected in erythrocyte N-glycans of normal cells or of other HEMPAS cases: The former contains polylactosaminoglycans and the latter contains hybrid-type oligosaccharides [19].
• The results of these experiments have demonstrated that regulation of both the C3 convertase of the alternative pathway and the membrane attack complex of complement by HEMPAS erythrocytes is aberrant [3].
• Freshly drawn blood samples (normal and HEMPAS Variant II-gal-) were separately incubated with P. falciparum from mannitol-synchronized cultures [5].
• These characteristics suggest that HEMPAS glycan has the nature of macroglycolipid [20].
• Congenital dyserythropoietic anaemia, types I and II: aberrant pattern of erythrocyte membrane proteins in CDA II, as revealed by two-dimensional polyacrylamide gel electrophoresis [21].

Other interactions of CDAN2

• Most recently a HEMPAS case has been identified as being defective in the gene encoding Golgi alpha-mannosidase II by using cDNA probe of alpha-mannosidase II [4].
• Short report: erythrocyte membranes from a patient with congenital dyserythropoietic anaemia type I (CDA-I) show identical, although less pronounced, glycoconjugate abnormalities to those from patients with CDA-II (HEMPAS) [22].
• The transport activities of AE1 and GLUT1 in HEMPAS erythrocytes were similar to those in normal controls [23].
• Therapeutic measures include interferon-alpha for CDA I, splenectomy for CDA II, and iron depletion for all individuals at risk for secondary hemochromatosis [24].
• Effect of CDA-II, urinary preparation, on lipofuscin, lipid peroxidation and antioxidant systems in young and middle-aged rat brain [25].

Analytical, diagnostic and therapeutic context of CDAN2

• By using anti-band 3 antibodies, immunogold electron microscopy revealed that band 3s are clustered in HEMPAS erythrocyte membranes [15].
• Upon intravenous infusion into rats, as much as 30% of the HEMPAS transferrin was cleared from the plasma circulation [16].
• 3H incorporation in band 3 and band 4.5 glycoproteins after treatment with galactose-oxidase/NaB[3H]4 is reduced in HEMPAS red cells suggesting a defective glycosylation of these proteins [26].
• Successful treatment of iron overload with phlebotomies in two siblings with congenital dyserythropoietic anemia--type II (CDA-II) [27].
• The proliferation kinetics of erythropoiesis and of myelopoiesis have been studied in a case of congenital dyserythropoietic anemia type II (HEMPAS) by means of quantitative 14-C autoradiography, Feulgen cytophotometry and 59-Fe ferrokinetics [28].

References