Transferrin mutations at the glycosylation site complicate diagnosis of congenital disorders of glycosylation type I.
Transferrin mutations at the glycosylation site complicate diagnosis of congenital disorders of glycosylation type I.
复制标题
DOI：
10.1007/s10545-011-9311-y
复制
发表时间：
2011-08
影响因子：
4.2
通讯作者：
Lefeber, Dirk J.
中科院分区：
文献类型：
--
作者：
Guillard, Mailys;Wada, Yoshinao;Hansikova, Hana;Yuasa, Isao;Vesela, Katerina;Ondruskova, Nina;Kadoya, Machiko;Janssen, Alice;Van den Heuvel, Lambertus P. W. J.;Morava, Eva;Zeman, Jiri;Wevers, Ron A.;Lefeber, Dirk J.
先天性糖基化障碍（CDG）形成由蛋白质和/或脂质的糖基化缺陷引起的一组代谢障碍。血清转铁蛋白的等电聚焦（IEF）是检测蛋白质N-糖基化异常的最常用的筛查方法。根据IEF特征，患者可分为CDG I型或CDG II型。已知转铁蛋白的几种蛋白变体导致等电点（pI）的偏移。在某些情况下，这些蛋白质变体与转铁蛋白糖型共迁移，这使解释复杂化。在2例血清转铁蛋白IEF谱异常的患者中，神经氨酸酶消化和随后的IEF显示提示CDG I型诊断的谱。然而，免疫纯化转铁蛋白的胰蛋白酶肽的质谱分析揭示了N-聚糖附着位点的新突变。在情况1中，鉴定了在第二糖基化位点具有突变p.Asn630Thr的肽，导致在IEF上的二唾液酸转铁蛋白位置处的额外条带。经神经氨酸酶消化后，在无唾液酸转铁蛋白位置发现一条带，与CDG I型患者无法区分。在病例2中，发现了一个带有突变p.Asn432His的肽段，这些结果表明转铁蛋白肽段的质谱分析在CDG I型诊断中的应用。
Congenital disorders of glycosylation (CDG) form a group of metabolic disorders caused by deficient glycosylation of proteins and/or lipids. Isoelectric focusing (IEF) of serum transferrin is the most common screening method to detect abnormalities of protein N-glycosylation. On the basis of the IEF profile, patients can be grouped into CDG type I or CDG type II. Several protein variants of transferrin are known that result in a shift in isoelectric point (pI). In some cases, these protein variants co-migrate with transferrin glycoforms, which complicates interpretation. In two patients with abnormal serum transferrin IEF profiles, neuraminidase digestion and subsequent IEF showed profiles suggestive of the diagnosis of CDG type I. Mass spectrometry of tryptic peptides of immunopurified transferrin, however, revealed a novel mutation at the N-glycan attachment site. In case 1, a peptide with mutation p.Asn630Thr in the 2nd glycosylation site was identified, resulting in an additional band at disialotransferrin position on IEF. After neuraminidase digestion, a single band was found at the asialotransferrin position, indistinguishable from CDG type I patients. In case 2, a peptide with mutation p.Asn432His was found. These results show the use of mass spectrometry of transferrin peptides in the diagnostic track of CDG type I.
登录
查看更多内容
DOI：
10.1016/j.jchromb.2006.02.028
发表时间：
2006-06-21
影响因子：
3
作者：
Wada, Yoshinao
通讯作者：
Wada, Yoshinao
影响因子：
7
作者：
Huelsmeier, Andreas J.;Paesold-Burda, Patricie;Hennet, Thierry
通讯作者：
Hennet, Thierry
DOI：
10.1016/0006-291x(92)92278-6
发表时间：
1992-12-15
影响因子：
3.1
作者：
WADA, Y;NISHIKAWA, A;TANIGUCHI, N
通讯作者：
TANIGUCHI, N
影响因子：
1.3
作者：
Wada, Yoshinao
通讯作者：
Wada, Yoshinao
影响因子：
4.2
作者：
Hahn, SH;Minnich, SJ;O'Brien, JF
通讯作者：
O'Brien, JF