Molecular characteristics
PIGW is an acyltransferase which transfers acyl-chain from the palmitoyl-CoA to the 2-position of the inositol ring of GlcN-PI to generate GlcN-(acyl)PI, the fourth step of the GPI biosynthesis. This step is necessary for the efficient synthesis of GPI, especially for the addition of ethanolamine phosphate to the third mannose. However, PIGW knockout cells express a small amount of GPI-anchored protein. This acyl chain is often removed by PGAP1 after GPI is attached to the precursor proteins in the ER.
Suspected pthogenecity
Mutations in PIGW cause decreased expression 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_178517.3)
validatad by the functional analysis or FACS analysis of blood
c.211A>C (p.Thr71Pro)/ c.499A>G(p.Met167Val)
c.460A>G (Arg154Gly) homo
c.106A>G (p.Arg36Gly) homo
c.77C>T (p.Leu26Ser) homo
c.173T>C (p.Leu58Pro)/ c.615_618del(p.Val206Glyfs*1)
c.200 C>T(p. Prp 67 Leu)/ c.230 C>T(P. Ser77Leu)
c.1463G>T(p.Cys488Phe) homo
c.458C>T (p.Pro153Leu)/ c.1450_1451del(p.Met484Valfs*15)
c.199C>G (p.Pro67Ala) homo
not validated
c.178G > A (p.Asp60Asn)/ c.462A > T(p.Arg154Gly)
Diagnostic testing
FACS analysis of a GPI-anchored protein, CD16 on the granulocytes can be the diagnostic testing for PIGW deficiency. It is decreased in the affected individuals compared to that in the healthy individuals. Affected individuals are partially deficient in PIGW activity, so levels of some GPI-anchored proteins such as CD59 and DAF are often within normal ranges.