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Review
. 2015 Jan;38(1):171-8.
doi: 10.1007/s10545-014-9752-1. Epub 2014 Aug 28.

Human genetic disorders involving glycosylphosphatidylinositol (GPI) anchors and glycosphingolipids (GSL)

Bobby G Ng  1 , Hudson H Freeze
Affiliations
Review

Human genetic disorders involving glycosylphosphatidylinositol (GPI) anchors and glycosphingolipids (GSL)

Bobby G Ng et al. J Inherit Metab Dis. 2015 Jan.

Abstract

Glycosylation - enabling genes are thought to comprise approximately 1-2 % of the human genome, thus, it is not surprising that more than 100 genetic disorders have been identified in this complex multi-pathway cellular process. Recent advances in next generation sequencing technology (NGS) have led to the discovery of genetic causes of many new disorders and importantly highlighted the broad phenotypes that occur. Here we will focus on two glycosylation pathways that involve lipids; glycosylphosphatidylinositol (GPI) anchors and glycosphingolipids (GSL) with emphasis on the specific gene defects, their biochemical properties, and their expanding clinical spectra. These disorders involve the intersection of two pathways: lipids and carbohydrates. Studies of both pathways were founded on structural biochemistry. Those methods and their more refined and sensitive descendants can both identify the specific genes that cause the disorders and validate the importance of the specific mutations.

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Figures

Fig. 1
Fig. 1
GPI anchor pathway in mammals. Schematic showing the mammalian GPI anchor pathway and the proteins involved for each step. Steps that involve genetic disorders are highlighted in Red. (Permission to use this figure was granted by The American Journal of Human Genetics)
Fig. 2
Fig. 2
GSL biosynthetic pathway for brain glycosphingolipids Sche-in red. Permission was granted to use a modified version of figure matic showing the major pathway for biosynthesis of brain 10.2 from chapter 10 Essentials of Glycobiology, second ed., CSHLP, glycosphingolipids. Steps that involve genetic disorders are highlighted 2009
See this image and copyright information in PMC

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