Molecular characteristics
PGAP3 is involved in the maturation of GPI-APs. In PGAP3 defective cells, GPI-APs are expressed with the abnormal structure, which cannot be localized on the lipid raft, the special domain of cell membrane, and GPI-APs cannot function properly.
Type of mutations
c.275G>A homo (p.Gly92Asp)
c.914A>G (p.Asp305Gly)
c.439dupC (p.Leu147fs)
c.314C>G homo (p.Pro105Arg)
c.845A>G homo (p.Asp282Gly)
etc.
Suspected pathophysiologic mechanism
In PGAP3 defective cells, GPI-APs are expressed with the abnormal structure. Those GPI-APs cannot be localized on the lipid raft and GPI-APs cannot function properly. GPI-APs play vital roles in numerous biological processes, such as neuronal development. Mislocalization of GPI -APs cause abnormal neuronal development, which leads to intellectual disability, developmental delay, and epilepsy.
Diagnostic testing
Usually, FACS analysis of a GPI-AP, CD16 on the granulocytes can be the diagnostic testing for GPI deficiency, however in PGAP3 deficiency, the decrease of CD16 on the granulocytes is not clear. Hyperphosphatasia is the good marker for the PGAP3 deficiency, but exome sequencing and the functional analysis of the mutations are necessary for diagnosis.