<P> Defects in the GPI - anchor synthesis occur in the rare acquired diseases such as paroxysmal nocturnal hemoglobinuria (PNH) and congenital diseases such as hyperphosphatasia with mental retardation syndrome (HPMRS). In PNH a somatic defect in blood stem cells, which is required for GPI synthesis, results in faulty GPI linkage of decay - accelerating factor (DAF) and CD59 in red blood cells . The most common cause of PNH are somatic mutations in the X-chromosomal gene PIGA . However, a PNH case with a germline mutation in the autosomal gene PIGT and a second acquired somatic hit has also been reported . Without these proteins linked to the cell surface, the complement system can lyse the cell, and high numbers of RBCs are destroyed, leading to hemoglobinuria . For patients with HPMRS, disease - causing mutations have been reported in the genes PIGV, PIGO, PGAP2 and PGAP3 . </P> <P> The variable surface glycoproteins from the sleeping sickness protozoan Trypanosoma brucei are attached to the plasma membrane via a GPI anchor . </P>

Where do gpi anchored proteins occur in membranes