Molecular characteristics
Biogenesis of GPI anchored proteins is a conserved post-translational mechanism in eukaryotes and is important for attaching these proteins to the cell membrane, which serve critical functions as adhesion molecules, receptors, complement regulators, enzymes and co-receptors in signal transduction pathways. There are at least 27 genes involved in biosynthesis and remodelling of GPI anchors. PIGM encodes the enzyme involved in the fifth step of GPI biosynthesis. Promoter region’s mutation in PIGM causes decreased expression of PIGM protein, leading to decreased levels of GPI-anchored proteins.
Suspected pthogenecity
This mutation in the Sp1 binding site of the promoter region caused the defect in PIGM expression, leading to decreased expression of GPI-anchored proteins in various tissues such as neuronal tissues, vascular endothelium, skin and hematopoietic cells. These affected individuals showed no developmental delay, suggesting that this defect may be compensated with some other binding sites or other transcriptional factors during developmental stage.