Molecular characteristics
PGAP1 is a deacylase that removes an acyl-chain from the inositol of GPI anchors in the endoplasmic reticulum immediately after attachment of GPI to the proteins. PGAP1 deficiency did not affect the surface expression of GPI-APs but expressed structurally abnormal GPI-APs with the acylated inositol.
Suspected pthogenecity
One of the characters of the GPI-APs is that their expression is regulated by being cleaved and released from the cell surface by some lipase. Those released proteins are also known to function on the different cells. PGAP1 deficient cells are resistant for the cleavage by lipase, which may cause the neurological abnormlities.
Mutations (NM_024989.3)
c.586_588del homo (p.L196del),
c.274_276del/c.921_925del (p.Pro92del /p.Leu308Asnfs*),
c.1952+1G>T homo splicing
c.1572T>A/c.1396C>T(p.Tyr524*/p.Gln466*)
c.1090-2A>G homo splicing
c.334_335InsA/c.1173G>C (p.A112fs/p.L391L)
Diagnostic testing
GPI-APs were cleaved and released from B lymphoblastoid cells from healthy individuals whereas GPI-APs on the cells from the affected person were totally resistant. FACS analysis of GPI-APs, such as CD59 and DAF, on the B lymphoblastoid cells with or without PIPLC treatment can be the diagnostic testing.
PGAP1