Molecular characteristics
PIGY 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 PIGY cause decreased expression levels of GPI-anchored proteins. PYURF and PIGY, 2 apparently unrelated proteins, are respectively the product of an upstream and a downstream ORF contained in a single bicistronic transcript.
Suspected pathophysiologic mechanism
The PIGY gene is involved in the first step of GPI biosynthesis, so PIGY 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_001042616.3)
c.137T>C (p.Leu46Pro) homo
c.-540G>A in the promoter region of Sp1 binding site, homo (due to cnLOH)
Diagnostic testing
FACS analysis of aGPI-anchored protein, CD16 on the granulocytes can be the diagnostic testing for PIGY deficiency. It is decreased in the affected individuals compared to that in the healthy individuals. Affected individuals are partially deficient in PIGY activity, so levels of some GPI-anchored proteins such as CD59 and DAF are often within normal ranges.