Molecular characteristics
PIGU is a component of GPI transamidase enzyme complex (GPIT) consist of PIGS, PIGT, GAA1, PIGU and PIGK, which recognizes the GPI attachment signal of the C-terminal of the precursor protein and processes and attaches GPI anchor. The mutations in PIGU cause decreased expression levels of GPI-APs.
Type of mutations
c.1149G>T (p.Asn383Lys)
c.209T>A (p.Ile70Lys)
Suspected pathophysiologic mechanism
PIGU is a component of GPIT and essential for the enzyme activity. PIGU deficient cells express decreased levels of GPI-APs. GPI-APs play vital roles in numerous biological processes, such as neuronal development. The decreased levels of GPI-APs cause abnormal neuronal development, which leads to intellectual disability, developmental delay, and epilepsy. Individuals with defect in GPIT genes commonly show bone abnormality sometimes with hypophosphatasia in severe cases.
Diagnostic testing
FACS analysis of a GPI-AP, CD16 on the granulocytes can be the diagnostic testing for PIGU deficiency. It is decreased in the affected individuals compared to that in the healthy individuals. Affected individuals are partially deficient in PIGU activity, so levels of some GPI-APs such as CD59 and DAF are often within normal ranges.
PIGU