Molecular characteristics
PIGN is the enzyme which transfer ethanolphosphate (EthP) to the first mannose, the seventh step of GPI biosynthesis. PIGN knockout cells partially express GPI-anchored proteins, so PIGN is important but not essential for GPI biosynthesis.
Mutations (NM_176787.4)
c.181G > T (p.Glu61*)/c.284G > A(p.Arg95Gln) validated (FACS)
c.406T>G (p.Trp136Gly)/ c.2576G>C (p.Ser859Thr) not validated
c.421dup (p.Ile141Asnfs*10) homo
c.505C>T(p.Gln169*)/ c.769 T>G (p.Phe257Val)
c.548_549 + 6del (Leu183fs )/ex5-7del
c.548_549 + 6del (Leu183fs )/ c.439A>T (p.Lys147*)
c.694A>T (p.Lys232*) homo
c.755A>T (p.Asp252Val) homo
c.709 G>A (p. Gly237Arg)/ c.2411_2412delTAinsAG (Ile804Lys)
c.782C>T (p.Ser261Phe)/ c.804G>C (p.Trp268Cys)
c.790G>A (p.Gly264Arg)/ c.932T>G (p.Leu311Trp)
c.808T>C (p.Ser270Pro)/ c.963G>A (p.Ala322Valfs*24 and Glu308Glyfs*2)
c.808T>C (p.Ser270Pro)/ex2-14del
c.808T>C (p.Ser270Pro)/ c.533T>G (p.Val178Gly) IRUD Akita Kubota
c.895 C > T(p.Gln299*)/ c.629 T > C (p.Leu210Ser)
c.932T>G (p.Leu311Trp)/ c.694A>T (p.Lys232*)
c.958_959insGTC (p.Asn320delinsSerHis) homo
c.963G >A (p.Gln321 Gln/ c.2427-2A >G (g. IVS26 -2A >G)
c.1109A >C (p.Gln370Pro)/ c.694A >T (p.Lys232*)
c.1261T>C (p.Cys421Arg)/ c.675-1G>C (g. IVS8 -1G>C
c.1357G>A (Gly453Arg)/ c.2557A>C (Thr853Pro)
c.1357G>A (Gly453Arg)/ c.128C>T(p.Ala43Val)
c.1434_1434+1delinsAA homo
c.1574+1G>A (g. IVS17+1G>A) homo
c.1694G >A (p.Arg565His)/ c.2663 T > C(p.Ile888Thr)/ c.963G > A (p.Q321Q)
c.1694G >A (p.Arg565His)/ c.343G > C(p.Gly115Arg)
c.1966C>T (p.Glu656*)/ c.1674+1G>C (g. IVS18 +1G>C)
c.1759C>T (p.Arg587*)/ c.163C>T (p.Arg55*)
c.2122C >T(p.Q708*)/ c.2557A>C (Thr853Pro)
c.2126G>A (p.Arg709Gln) homo
c.2126G>A (p.Arg709Gln)/ c.654T>G (p.His218Gln)
c.2340T>A (Tyr780*)/ c.1434+5G>A (g. IVS17+5G>A)
c.2679C>G (p.Ser893Arg) homo
c.2759_2760del (p.Leu920fs*3)/ c.1172 + 1G >A(g. IVS14 +1G>A)
5kb del (ex5-7) homo
c.2332delC(p.778fs)/ c.761A>T( p.Lys254Ile)
Suspected pathophysiologic mechanism
The PIGN gene is involved in the eighth step of GPI biosynthesis, so PIGN 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.
Diagnostic testing
FACS analysis of GPI-AP, CD16 on the granulocytes can be the diagnostic testing for PIGN deficiency. It is decreased in the affected individuals compared to that in the healthy individuals. Affected individuals are partially deficient in PIGN activity, so CD59 or DAF expression is often within normal ranges.