Molecular characteristics

Molecular characteristics
PIGQ encodes one component of the GPI-N-acetylglucosaminyltransferase (GIP-GnT) complex composed of the seven proteins (PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY and DPM2), which is involved in the first step of GPI biosynthesis. The mutations in PIGQ cause decreased expression levels of GPI-anchored proteins.

Suspected pathophysiologic mechanism
The PIGQ gene is involved in the first step of GPI biosynthesis, so PIGQ deficient cells express decreased levels of GPI-anchored proteins. 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 can lead to intellectual disability, developmental delay, and epilepsy.

Mutations (NM_004204.5)
c.690–2A>G (IVS2-2 A>G) homo
c.1199_1201delACT (p.Tyr400del)/c.968_969delTG (p.Leu323Profs*119)
c.619C>T (p.Arg207*) homo
c.1611del (p.Arg538Alafs*24) homo
c.1199_1201de l (p.Tyr400del)/ c.942+1G>A (IVS4+1G>A)  
c.1199_1201de l (p.Tyr400del)/c.1578_1579del (p.Gln527Alafs*75)
c.1130_1168del (p.Ala377_Ser389del)/ c.1345G>C (p.Gly449Arg)
c.49G>A (p.Gly17Arg)/ c.942+1G>A (IVS4+1G>A)
c.1670del (p.Gly557Aspfs*4) homo
c.1631dupA (p.Tyr544fs*79) homo 

Diagnostic testing
FACS analysis of a GPI-anchored protein, CD16 on the granulocytes can be the diagnostic testing for PIGQ deficiency. It is decreased in the affected individuals compared to that in the healthy individuals. Affected individuals are partially deficient in PIGQ activity, so levels of some GPI-anchored proteins such as CD59 and DAF are often within normal ranges.