Genetic complementation reveals a novel human congenital disorder of glycosylation of type II, due to inactivation of the Golgi CMP-sialic acid transporter
Genetic complementation reveals a novel human congenital disorder of glycosylation of type II, due to inactivation of the Golgi CMP-sialic acid transporter
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DOI：
10.1182/blood-2004-09-3509
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发表时间：
2005-04-01
期刊：
影响因子：
20.3
通讯作者：
Mollicone, R
中科院分区：
文献类型：
--
作者：
Martinez-Duncker, I;Dupré, T;Mollicone, R
我们已经在Lec2细胞的胞苷单磷酸(CMP)-唾液酸转运基因6内含子（IVS6 + 1G > a）的供体剪接位点上发现了一个纯合子G > a替代，这是导致其亚洲表型的突变。这些细胞被用于互补研究，以测试2 cmp -唾液酸转运体cDNA等位基因在多形核细胞上表达缺失的患者的活性。两个患者等位基因均未获得互补，而在转染相应的人类野生型转录物的Lec2细胞中获得了唾液化表型的完全恢复。一个患者等位基因的双微缺失导致327位过早终止密码子失活，另一个等位基因的剪接突变导致130碱基对（bp）缺失和684位过早终止密码子缺失，这被认为是该疾病的因果缺陷。在母体中发现了内含子6中的一个4碱基插入，这可能是剪接突变的原因。我们认为这种缺陷是一种新的先天性IIf型糖基化障碍（CDG），影响cmp -唾液酸进入高尔基体的运输。(c) 2005年由美国血液学会出版。
We have identified a homozygous G > A substitution in the donor splice site of intron 6 (IVS6 + 1G > A) of the cytidine monophosphate (CMP)-sialic acid transporter gene of Lec2 cells as the mutation responsible for their asialo phenotype. These cells were used in complementation studies to test the activity of the 2 CMP-sialic acid transporter cDNA alleles of a patient devoid of sialyl-Le(x) expression on polymorphonuclear cells. No complementation was obtained with either of the 2 patient alleles, whereas full restoration of the sialylated phenotype was obtained in the Lec2 cells transfected with the corresponding human wild-type transcript. The inactivation of one patient allele by a double microdeletion inducing a premature stop codon at position 327 and a splice mutation of the other allele inducing a 130-base pair (bp) deletion and a premature stop codon at position 684 are proposed to be the causal defects of this disease. A 4-base insertion in intron 6 was found in the mother and is proposed to be responsible for the splice mutation. We conclude that this defect is a new type of congenital disorder of glycosylation (CDG) of type IIf affecting the transport of CMP-sialic acid into the Golgi apparatus. (c) 2005 by The American Society of Hematology.