PGAP3 deficiency is caused by germline mutation in PGAP3. PGAP3 (Post-GPI Attachment To Proteins 3) is involved in the first step of fatty-acid remodeling of GPI-APs. Firstly, PGAP3 removes the unsaturated lipid chain at sn-2 position, followed by addition of a saturated lipid chain in the second step. Thus, in PGAP3 defective cells, GPI-APs are expressed with the abnormal structure with unsaturated fatty-acid chain at sn-2 position. Those GPI-APs cannot be localized on the lipid raft and GPI-APs cannot function properly. GPI-APs serve critical functions as adhesion molecules, receptors, complement regulators, enzymes and co-receptors in signal transduction pathways. Mislocalization of GPI-APs causes mainly neurological disorders such as intellectual disability, developmental delay, muscular hypotonia and epilepsy. The PGAP3 gene is located on chromosome 17q12 and PGAP3 deficiency is an autosomal recessive disorder. PGAP3 is one of the responsible genes for Mabry syndrome (HPMRS, Hyperphosphatasia and mental retardation syndrome).
PGAP3