Molecular characteristics

Molecular characteristics
PIGO is the catalytic subunit of PIGO-PIGF enzyme complex which attaches ethanolamine phosphate to the third mannose of GPI. Through this ethanolamine, GPI is attached to C-terminal of the precursor protein by GPI transamidase complex. Thus, PIGO is necessary for the expression of the GPI-APs. The mutations in PIGOcause decreased expression levels of GPI-APs.

Type of mutations
c.2869C>T (p.Leu957Phe)
c.3069+5G>A (Splice defect)
c.2361dup (p.Thr788Hisfs*5)
c.2869C>T (p.Leu957Phe)
c. 355C>T (p. Arg119trp)
c.2497_2498del (frameshift)

Suspected pathophysiologic mechanism
The PIGO attaches ethanolamine phosphate to the third mannose of GPI. Through this ethanolamine, GPI is attached to C-terminal of the precursor protein by GPI transamidase complex, so PIGO deficient cells express decreased levels of GPI-APs. GPI-APs play vital roles in numerous biological processes, such as neuronal development. The decreased levels of GPI-APs 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 PIGO deficiency. It is decreased in the affected individuals compared to that in the healthy individuals. Affected individuals are partially deficient in PIGO activity, so levels of some GPI-APs such as CD59 and DAF are often within normal ranges.