Molecular characteristics

Molecular characteristics
PIGG is catalytic component of an enzyme complex, PIGG/PIGF, which transfers ethanolamine phosphate (EtNP) to the second mannose (Man) to generate EtNP-Man-(EtNP)Man-(EtNP)Man-Glucosamine-PI, the tenth step of the GPI biosynthesis. This second EtNP is removed by PGAP5 after GPI is attached to the precursor protein in the ER.  Thus, the PIGG deficient cells express the GPI-anchored proteins at normal level with the normal structure on the cell surface. It has been believed that EtNP on the third Man is always used for the bridge to the C-terminal of the proteins. However, our recent analysis revealed that some proteins preferentially use the EtNP on the second Man for the bridge to the proteins.
The blood-type antigen with high frequency called Emm antigen has been known broadly and recent analysis revealed that the PIGG deficient individuals produce natural antibody against this antigen. Different from other IGDs, affected individuals with null mutations of PIGG can survive. Recently, we reported that GPIs without attachment of proteins (free GPI) is expressed on the cell surface of the blood cells. Among them, GPI with EtNP on the second Man and with fourth Man is abundantly expressed in the healthy individuals. Some PIGG deficient individuals produce the natural antibodies against this structure (Emm antigen). It should be noted when blood transfusion is necessary for the PIGG deficient patients.

Suspected pthogenecity
Mutations in PIGG may cause the decreased expression of some GPI-anchored proteins in neuronal cells. 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_001127178.1)
c.928C>T (p.Gln310*) homo
c.2005C>T (p. Arg669Cys)/ microdeletion (WHS)
c.2005C>T (p.Arg669Cys)/ c.2758_2761del (p.Cys920Serfs)
c.2261+1G>C homo
c.1640G>A (p.W547*) homo
c.2624_2625delTA  (p.Leu875*) homo
c.413A>G (p.Asn138Ser) homo
c.717G>A (p.Met239Ile) homo
c.2041C>T (p.Arg681Trp)/ c.2088G>C (p.Glu696Asp)
c.2375_2360delACTT (p.Asp786Alafs6*)/c.1591G>A (p.Val531Met)
c.2552A>C (p.Gln851Pro) homo
c.371C>T (p.Thr124Met)/ c.1490C>T (p.Ser497Leu)
c.832G>A (p.Gly278Arg)/ c.812T>G (p.Met271Arg)
c.910C>T (p.Arg304*)/c.1030A>C  (p.Met344Leu)
c.2802C>A (p.Tyr934*) homo
c.129_130insCC (p.Ala46Glnfs*28) homo
c.809G>A (p.Gly270Asp) homo
c.1515G>A (Trp505*) homo
c.640C>T (p. His214Tyr) homo
c.901+1delG (g. IVS5+1delG) homo
517639G>A (p.Arg658Gln) homo

Diagnostic testing
Whole exome sequence is necessary for diagnosis.