Zdebska Ewa, Bader-Meunier Brigitte, Schischmanoff Pierre-Olivier, Dupré Thierry, Seta Nathalie, Tchernia Gil, Kościelak Jerzy, Delaunay Jean
Service d'Hématologie, d'Immunologie et de Cytogénétique, Hôpital de Bicêtre, 78 rue du Général-Leclerc; 94275 Le Kremlin-Bicêtre, France.
Pediatr Res. 2003 Aug;54(2):224-9. doi: 10.1203/01.PDR.0000072327.55955.F7. Epub 2003 May 7.
A description is provided of the clinical presentation in an infant of the recently described congenital disorder of glycosylation type Ig, and the changes affecting glycosylation of red cell membrane band 3, the anion exchanger. It has been shown that the condition stems from a homozygous mutation within the human ortholog of yeast ALG12 gene, which encodes a dolichol-P-mannose:Man7GlcNAc2-PP-dolichol alpha,1-6 mannosyltransferase of the endoplasmic reticulum. The clinical phenotype included prominent central and peripheral manifestations in the CNS. Although the infant studied had no anemia, band 3 abnormally separated into two fractions upon electrophoresis. The chemical composition of the glycans of both fractions was analyzed in detail. The fraction with low electrophoretic mobility was moderately hypoglycosylated (by 27%) and its mannose content was normal. The fraction with high electrophoretic mobility was deeply carbohydrate deficient (by 64%) and had 1 mol mannose in excess but only three residues of N-acetylglucosamine. Glycophorin A was hypoglycosylated with respect to O-linked glycans. Glycosphingolipids of red cells were normal. We suggest that the incomplete biosynthesis of the N-linked glycan of band 3 was largely caused by the persistence of the 3-linked mannose residue on the 6-mannose arm of the trimannosyl moiety of the glycoprotein. It is remarkable that the changes recorded in band 3 have no clinical consequences. Band 3 alteration might serve as an additional indicator (some serum N-glycoproteins of hepatic origin are also indicative) of the congenital disorder of glycosylation type Ig.
本文描述了一名患有最近描述的糖基化先天性紊乱I型的婴儿的临床表现，以及影响红细胞膜带3（阴离子交换蛋白）糖基化的变化。研究表明，该病症源于酵母ALG12基因人类直系同源基因中的纯合突变，该基因编码内质网的一种多萜醇-P-甘露糖：Man7GlcNAc2-PP-多萜醇α,1-6甘露糖基转移酶。临床表型包括中枢神经系统明显的中枢和外周表现。尽管所研究的婴儿没有贫血，但带3在电泳时异常分离为两个部分。对这两个部分聚糖的化学组成进行了详细分析。电泳迁移率低的部分糖基化程度中等降低（降低27%），其甘露糖含量正常。电泳迁移率高的部分碳水化合物严重缺乏（降低64%），有1摩尔过量的甘露糖，但只有三个N-乙酰葡糖胺残基。血型糖蛋白A的O-连接聚糖糖基化程度降低。红细胞的糖鞘脂正常。我们认为，带3的N-连接聚糖生物合成不完全主要是由于糖蛋白三甘露糖部分6-甘露糖臂上3-连接甘露糖残基的持续存在。值得注意的是，带3中记录的变化没有临床后果。带3的改变可能作为糖基化先天性紊乱I型的一个额外指标（一些肝脏来源的血清N-糖蛋白也有指示作用）。
