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N- and O-glycan analysis for the detection of glycosylation disorders
Egyptian Journal of Medical Human Genetics Pub Date : 2021-01-06 , DOI: 10.1186/s43042-020-00117-w
Amr Sobhi Gouda , Azza Fahmy Elbaz , Thierry Dupré , Ola Sayed Mohamed Ali , Maha Saad Zaki , Ekram Maher Fateen

Congenital disorders of glycosylation (CDGs) are defined as a group of several rare autosomal recessive inborn errors of metabolism that affect the glycosylation of many proteins and/or lipids. Variable clinical presentation is very characteristic for all types of CDGs; symptoms include severe neurological manifestations that usually start in the neonatal period and cause aggressive irreversible neurological damage. These disorders are usually misdiagnosed as other non-inheritable disorders or remain undiagnosed for a long time, leading to severe neurological complications. The diagnosis of CDGs is quite tedious due to their diverse clinical presentation. In Egypt, there is still no available screening programme to detect CDGs in patients at a young age. Therefore, the need for a reliable rapid test that uses a small sample size has emerged. This study included 50 suspected subjects and 50 healthy controls with matching age and sex. Western blotting and liquid chromatography-tandem mass spectrometry were used for the analysis of N- and O-glycans, respectively. The study detected 9 patients with hypoglycosylation (18%). Eight of the nine patients showed abnormal separation of N-glycoproteins using Western blotting indicative of reduced glycosylation (16% of the study subjects and 89% of the subjects with hypoglycosylation). Only one of the nine patients showed a decreased level of sialyl-T-antigen with a normal T-antigen level leading to an increased T/ST ratio (2% of study subjects and 11% of the subjects with hypoglycosylation). Although N- and O-glycan analysis did not determine the underlying type of CDG, it successfully detected hypoglycosylation in 9 clinically suspected patients (18% of the studied subjects). All detected CDG cases were confirmed by molecular analysis results of mutations causing 4 different types of congenital disorders of glycosylation.

中文翻译:

用于检测糖基化障碍的 N- 和 O-聚糖分析

先天性糖基化障碍 (CDGs) 被定义为一组罕见的常染色体隐性先天性代谢缺陷,影响许多蛋白质和/或脂质的糖基化。所有类型的 CDG 都具有不同的临床表现。症状包括严重的神经系统表现,通常在新生儿期开始并导致不可逆转的侵袭性神经系统损伤。这些疾病通常被误诊为其他非遗传性疾病或长时间未确诊,导致严重的神经系统并发症。由于 CDG 的多种临床表现,其诊断非常繁琐。在埃及,仍然没有可用的筛查计划来检测年轻患者的 CDG。因此,出现了对使用小样本量的可靠快速测试的需求。该研究包括年龄和性别相匹配的 50 名疑似受试者和 50 名健康对照。蛋白质印迹法和液相色谱-串联质谱法分别用于分析 N-和 O-聚糖。该研究检测到 9 名低糖基化患者 (18%)。九名患者中有八名使用蛋白质印迹显示 N-糖蛋白的异常分离,表明糖基化减少(16% 的研究对象和 89% 的低糖基化对象)。9 名患者中只有 1 名显示唾液酸 T 抗原水平降低,而 T 抗原水平正常,导致 T/ST 比值增加(2% 的研究对象和 11% 的低糖基化对象)。尽管 N- 和 O-聚糖分析不能确定 CDG 的潜在类型,它在 9 名临床疑似患者(占研究对象的 18%)中成功检测到低糖基化。所有检测到的CDG病例均通过引起4种不同类型的糖基化先天性疾病的突变的分子分析结果证实。
更新日期:2021-01-06
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