Molecular characteristics
PGAP2 is involved in the maturation of GPI-APs in the Golgi. In PGAP2 defective cells, GPI-APs are expressed with abnormal structure, which are released from the cell surface, leading to decreased expression of GPI-APs.
Type of mutations
c.296A>G homo(p.Tyr99Cys)
c.539G>C homo(p.Arg77Pro)
c.46C>T(p.Arg16Trp)
c.479C>T (p.Thr160Ile)
c.380T>C homo(p.Leu127Ser)
etc.
Suspected pathophysiologic mechanism
In PGAP2 defective cells, GPI-APs are expressed with abnormal structure, which are released from the cell surface, leading to decreased expression of GPI-APs. GPI-anchored proteins play vital roles in numerous biological processes, such as neuronal development. The decreased levels of GPI anchored proteins cause abnormal neuronal development, which leads to intellectual disability, developmental delay, and epilepsy.
Diagnostic testing
FACS analysis of a GPI-AP, CD16 on the granulocytes can be the diagnostic testing for PGAP2 deficiency. It is decreased in the affected individuals compared to that in the healthy individuals. Affected individuals are partially deficient in PGAP2 activity, so levels of some GPI-APs such as CD59 and DAF are often within normal ranges.