Inherited glycosylphosphatidylinositol defects cause the rare Emm-negative blood phenotype and developmental disorders.
Glycosylphosphatidylinositol (GPI) is a glycolipid that anchors more than 150 proteins to the cell surface. Pathogenic variants in several genes that participate in GPI biosynthesis cause inherited GPI deficiency (IGD) disorders. Here, we reported that homozygous null alleles of PIGG, a gene involved in GPI modification, are responsible for the rare Emm-negative blood phenotype. Using a panel of K562 cells defective in both the GPI-transamidase and GPI remodeling pathways, we demonstrate that the Emm antigen, whose molecular basis has remained unknown for decades, is carried only by free GPI and that its epitope is composed of the second and third ethanolamine of the GPI backbone. Importantly, we show that the decrease in Emm expression in several IGD patients is indicative of GPI defects. Overall, our findings establish Emm as a novel blood group system and have important implications for understanding the biological function of human free GPI.
Authors: Romain Duval, Gaël Nicolas, Alexandra Willemetz, Yoshiko Murakami, Mahmoud Mikdar, Cedric Vrignaud, Hisham Megahed, Jean-Pierre Cartron, Cecile Masson, Samer Wehbi, Berengere Koehl, Marie Hully, Karine Siquier, Nicole Chemaly, Agnes Rotig, Stanislas Lyonnet, Yves Colin, Giulia Barcia, Vincent Cantagrel, Caroline Le Van Kim, Olivier Hermine, Taroh Kinoshita, Thierry Peyrard, Slim Azouzi