FIGURE 3 Mechanism of AGE-RAGE pathway and associated genes in severe patient with Class IV mutation. AGE ligands bind to its receptors called RAGE. RAGE induced NAPDH production triggers ROS reactive oxygen species (ROS) that is resulted in PI3K-AKT signaling pathway activation and NOS3 mediated apoptosis. Also, PI3K-AKT signaling pathway trigger NF-kappa B signaling pathway and induce inflammation mechanism in the severe sibling (Genes associated with AGE-RAGE signaling pathway in diabetic complications are shown in bold.).