Molecular characteristics

Molecular characteristics
PIGA encodes catalytic 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 PIGA cause decreased expression levels of GPI-APs.
Type of mutations
c.56G>A (p.Arg19Gln)
c.68dupG (p.Ser24Lysfs*3)
c.76dupT (p.Tyr26Leufs*3)
c.110T>C (p.37Met>Thr)
c.145G>A (p.Val49Met)
c.191G>A (p.Gly64Glu)
c.212C>T (p.Thr71Ile)
c.229C>G (p.Arg77Gly)
c.230G>T (p.Arg77Leu)
c.236G>T (p.Gly79Val)
c.241C>T (p.Arg81Cys)
c.242G>A (p.Arg81His)
c.248T>C (p.Leu83Pro)
c.269A>G (p.Tyr90Cys)
c.278C>T (p.Pro93Leu)
c.293A>C (p.Tyr98Ser)
c.328_330del (p.Leu110del)
c.347T>C (p.Ile116Thr)
c.355C>T (p.Arg119Trp)
c.356G > A (p.Arg119Gln)
c.368C>T (p.Thr123Met)
c.391T>C (p.Phe131Leu)
c.395C>G (p.Ser132Cys)
c.403G>T (p.Ala135Val)
c.424G>A (p.Ala142Thr)
c.481G>A (p.Asp161Asn)
c.535A>T (p.Asn179Tyr)
c.542T>G (p.Ile181Ser)
c.565A>G (p.Lys189Glu)
c.616A>T (p.Ile206Phe)
c.652G>A (p.Asp218Asn)
c.971G>T (p.Cys324Phe)
c.986T>C (p.Val329Ala)
c.989G>A (p.Ser330Asn)
c.1030_1032delCCT (p.Leu344del)
c.1031T>C (p.Leu344Pro)
c.1064T>C (p.Leu355Ser)
c.1097T>C (p.Leu366Pro)
c.1298T>A (p.Val433Asp)
c.1234C>T (p.Arg412Xaa)
c.1352T>C (p.Ile451Thr)
c.1354G>T (p.Asp452Tyr)
c.1386_1393dup (p.Thr465Metfs*30)
g.15342986C>T (p.Ser330Asn)

Suspected pathophysiologic mechanism
The PIGA gene is involved in the first step of GPI biosynthesis, so PIGA 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 leads to intellectual disability, developmental delay, and epilepsy.

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