Research in Japan Has Contributed to the Understanding of GPI Anchor Deficiency
Glycosylphosphatidylinositol (GPI) anchors more than 200 surface proteins to the plasma membrane. Therefore, GPI deficiency causes severe effects. Twenty-six genes involved in GPI biosynthesis have been cloned and among them PIGA carries the first step. The finding, that a Piga knockout mouse is lethal, indicates that GPI is essential for ontogenesis. Even the tissue-specific knockout of the Piga gene causes severe defects, e.g., a keratinocyte-specific knockout causes death soon after birth and an oocyte-specific knockout causes infertility. These lines of evidence suggest that only partial GPI deficiency causes disease. Among 26 GPI biosynthesis genes, 4 genes, DPM1, DPM2, DPM3 and SL15 (MPDU1), are also involved in biosynthesis of N-glycan. A defect in these genes causes congenital deficiencies of glycosylation (CDG). Deficiencies of DPM1 and SL15 (MPDU1) have been reported and called CDG-Ie and CDG-If, respectively. Both of these deficiencies are partial and the symptoms of these patients seem to be mainly caused by defective N-glycosylation.
KeywordsSomatic Mutation Aplastic Anemia Portal Vein Thrombosis Paroxysmal Nocturnal Hemoglobinuria Decay Accelerate Factor
Unable to display preview. Download preview PDF.