Charuk J H, Tan J, Bernardini M, Haddad S, Reithmeier R A, Jaeken J, Schachter H
Department of Medicine, University of Toronto, Canada.
Eur J Biochem. 1995 Jun 1;230(2):797-805. doi: 10.1111/j.1432-1033.1995.0797h.x.
Carbohydrate-deficient glycoprotein syndromes (CDGS) are a family of multisystemic congenital diseases resulting in underglycosylated glycoproteins, suggesting defective N-glycan assembly. Fibroblast extracts from two patients with a recently described variant of this disease (CDGS type II) have previously been shown to have over 98% reduced activity of UDP-GlcNAc:alpha-6-D-mannoside beta-1,2-N-acetylglucosaminyltransferase II [GlcNAc-TII; Jaeken, J., Schachter, H., Carchon, H., De Cock, P., Coddeville, B. & Spik, G. (1994) Arch. Dis. Childhood 71, 123-127]. We show in this paper that mononuclear cell extracts from one of these CDGS type-II patients have no detectable GlcNAc-TII activity and that similar extracts from 12 blood relatives of the patient, including his father, mother and brother, have GlcNAc-TII levels 32-67% that of normal levels (average 50.1% +/- 10.7% SD), consistent with an autosomal recessive disease. The poly(N-acetyllactosamine) content of erythrocyte membrane glycoproteins bands 3 and 4.5 of this CDGS patient were estimated, by tomato lectin blotting, to be reduced by 50% relative to samples obtained from blood relatives and normal controls. Similar to patients with hereditary erythroblastic multinuclearity with a positive acidified-serum lysis test (HEMPAS), erythrocyte membrane glycoproteins in the CDGS patient have increased reactivities with concanavalin A, demonstrating the presence of hybrid or oligomannose carbohydrate structures. However, bands 3 and 4.5 in HEMPAS erythrocytes have almost complete lack of poly(N-acetyllactosamine). Furthermore, CDGS type-II patients have a totally different clinical presentation and their erythrocytes do not show the serology typical of HEMPAS, suggesting that the genetic lesions responsible for these two diseases are possibly different.
糖基缺乏性糖蛋白综合征（CDGS）是一类多系统先天性疾病，会导致糖蛋白糖基化不足，提示N-聚糖组装存在缺陷。先前已证明，两名患有该疾病最近描述变体（II型CDGS）的患者的成纤维细胞提取物中，UDP-GlcNAc:α-6-D-甘露糖苷β-1,2-N-乙酰葡糖胺基转移酶II [GlcNAc-TII；杰克恩，J.，沙克特，H.，卡尔雄，H.，德科克，P.，科德维尔，B. & 斯皮克，G.（1994年）《儿童疾病档案》71卷，123 - 127页] 的活性降低了98%以上。我们在本文中表明，其中一名II型CDGS患者的单核细胞提取物中未检测到GlcNAc-TII活性，并且该患者的12名血亲（包括其父亲、母亲和兄弟）的类似提取物中，GlcNAc-TII水平为正常水平的32% - 67%（平均50.1% ± 10.7%标准差），这与常染色体隐性疾病一致。通过番茄凝集素印迹法估计，该II型CDGS患者红细胞膜糖蛋白带3和带4.5的聚（N-乙酰乳糖胺）含量相对于从血亲及正常对照获取的样本降低了50%。与遗传性红细胞多核症伴酸化血清溶血试验阳性（HEMPAS）患者相似，该II型CDGS患者红细胞膜糖蛋白与伴刀豆球蛋白A反应性增加，表明存在杂合或低聚甘露糖碳水化合物结构。然而，HEMPAS红细胞中的带3和带4.5几乎完全缺乏聚（N-乙酰乳糖胺）。此外，II型CDGS患者有完全不同的临床表现，且其红细胞未表现出HEMPAS典型的血清学特征，这表明导致这两种疾病的基因损伤可能不同。
