Transferrin variants: Pitfalls in the diagnostics of Congenital disorders of glycosylation
Transferrin variants: Pitfalls in the diagnostics of Congenital disorders of glycosylation
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DOI：
10.1016/j.clinbiochem.2014.09.022
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发表时间：
2015-01-01
影响因子：
2.8
通讯作者：
Marquardt, Thorsten
中科院分区：
文献类型：
--
作者：
Zuhlsdorf, Andrea;Park, Julien Heinrich;Marquardt, Thorsten
目的：在疑似先天性糖化异常的病例中，转铁蛋白变异可阻碍诊断过程，从而影响N-糖基化。此外，它们还会影响碳水化合物缺乏的转铁蛋白作为慢性酒精滥用的生物标志物的使用，在慢性酒精滥用中，Asialo-Transferrin和Disialo-Transferrin增加。我们提出了一种新的转铁蛋白变异体，并对实验室中发现的转铁蛋白突变进行了概述。设计和方法：采用等电聚焦和高效液相色谱等标准诊断程序以及神经氨酸酶消化糖链和电喷雾飞行时间质谱仪(ESI-TOF MS)对疑似CDG患者的血液样本进行分析。结果：鉴定出4个已知的转铁蛋白变异体和一个以前未报道的转铁蛋白变异体。神经氨酸酶消化和ESI-TOF MS显示转铁蛋白分子电荷的变化，而糖基化状态正常。结论：转铁蛋白变异是诊断CDG的陷阱。发现的变异体改变了转铁蛋白分子的电荷，从而影响了标准的诊断程序。神经氨酸酶消化以及ESI-TOF MS可以在实验室环境中识别变异和突变。(C)2014年加拿大临床化学家学会。爱思唯尔公司出版，版权所有。
Objectives: Transferrin variants can hinder the diagnostic process in cases of suspected Congenital disorders of glycosylation which affect N-Glycosylation. In addition they can impair the use of Carbohydrate deficient Transferrin as a biomarker for chronic alcohol abuse, in which Asialo-Transferrin and Disialo-Transferrin are increased. We present a novel transferrin variant as well as an overview of transferrin mutations found at our laboratory.Design and methods: Blood samples from patients with suspected CDG were analyzed using the standard diagnostic procedures of Isoelectric focusing and High-performance liquid chromatography as well as the additional procedures of neuraminidase digestion of glycans and Electrospray ionization time-of-flight mass spectrometry (ESI-TOF MS).Results: Four known and one previously unreported transferrin variants were identified. Neuraminidase digestion and ESI-TOF MS revealed changes in charge of the transferrin molecules while the glycosylation status was found to be normal.Conclusion: Transferrin variants are pitfalls in the diagnostics of CDG. The found variants change the charge of the transferrin molecule, thus affecting the standard diagnostic procedures. Neuraminidase digestion as well as ESI-TOF MS can identify variants and mutations in a laboratory context. (C) 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.