ANALYSIS OF N-LINKED GLYCOFORM VARIANTS IN CONGENITAL DISORDERS OF GLYCOSYLATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 哺乳动物中超过一半的蛋白质，特别是在人类中，通过连接到天冬氨酸(N-连接的多糖)或丝氨酸/苏氨酸(O-连接的多糖)以及有时也与其他位点连接而糖基化。参与糖链组装的糖苷酶和糖基转移酶的缺失或表达减弱可导致严重的疾病，现在统称为“先天性糖基化紊乱(CDGs)”。一些CDG中的异常通路已经被定义，但许多新的病例正在被识别。有时很难确定所产生的多糖的特定结构，特别是当修饰或存在多条途径或不完全外露导致糖基化混合物的产生时。该资源与弗里德教授和他的同事合作，解开了糖链结构，从而在最近的一个病例中推断出遗传异常，该病例导致了一种新的先天性糖基化紊乱，IIH型，涉及COG8缺陷。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. More than half of the proteins in mammals, specifically in humans, are glycosylated through linkages to asparagine (N-linked glycans) or serine/threonine (O-linked glycans) and ocassionally other sites as well. The absence or diminished expression of glycosidases and glycosyl transfereases that are involved in the assembly of glycans can lead to severe disease, now generically referred to as "congenital disorders of glycosylation (CDGs). The aberrant pathways in some CDGs have been defined, but numerous new cases are being recognized. It is sometimes difficult to determine the specific structures of the resulting glycans, especially when the modification or presence of multiple pathways or incomplete penetrance of the disorder leads to the production of glycosylation mixtures. The Resource collaborated with Prof. Freeze and his colleagues to unravel the glycan structures and thereby to deduce the genetic aberration in a recent case that resulted in the definintion of a new congenital disorder of glycosylation, type IIh, that involves a deficiency of COG8.