Schematic diagrams of states of IMPs and the skeletal network in RBCs of normal and the 4.1 (−) Madrid case. The upper and the middle portions indicate the sizes and distribution patterns of IMPs in normal (left) and the 4.1 (−) Madrid case (right). The clustering of the normal-sized IMPs is evident in the 4.1 (−) Madrid case. The bottom portions represent the states of the skeletal network of normal (left) and the 4.1 (−) Madrid case (right). (•) Antispectrin antibody-conjugated immunogold particles; (○) antiankyrin antibody-conjugated immunogold particles. The skeletal network in the 4.1 (−) Madrid case is markedly disrupted, which is proven by the abnormal distribution of the immunogold particles for spectrin. Ankyrin tends to cluster more than spectrin in the 4.1 (−) Madrid case.