Six individuals from three unrelated families with bi-allelic PIGS biosynthesis mutations were studied. Missense mutations, loss of function, and splicing mutations were found. The PIGS gene encodes an endoplasmic reticulum transmembrane protein. This protein is part of the GPI-lipid-anchor transamidase complex involved in the attachment of the GPI anchor to the C- terminus of precursor proteins in the endoplasmic reticulum. Functional studies on individuals with PIGS mutations show a decrease in GPI-anchored proteins (GPI-Aps) at the cell surface demonstrating a defect in the biosynthesis of GPI-Aps. Approximately one in every 200 mammalian proteins is a GPI-Aps. These proteins are important for neurological development and function, embryogenesis, immune response, and signal transduction.
PIGS