[Cytoskeleton anomalies in disorders of red cell membrane proteins]

Cytoskeletal abnormalities in red cells were studied in 250 patients at our laboratory, especially on hereditary elliptocytosis (HE), hereditary spherocytosis (HS), and band 4.2 anomalies. First of all, on HE, we have found two patients of a dominantly-inherited trait of a new beta-spectrin variant with 216 kDa peptide. The contents of abnormal beta'-spectrin to the total spectrins were 7.6% in propositus, and 10.5% in her mother. As a functional abnormality, abnormal alpha beta'-spectrin dimer could not be converted to tetramer in both patients. Thus, our patients may differ from HE Nice. Secondarily, the causal relationship between red cell ankyrin and spectrin was studied on a typical HS case with abnormal chromosome, del (8p11.2-8p21.1). In this case, the deleted genetic locus was involved with loci of genes for SPH1 and ankyrin. The contents of ankyrin and other red cell membrane proteins, however, appeared to be normal on SDS-PAGE. In addition, as a unique disorder in Japan, unrelated five cases of membrane protein 4.2 deficiency were found at our laboratory. In these cases, the characteristic features were; 1) clinically uncompensated hemolysis, 2) ovalostomatocytosis, 3) markedly decreased deformability of the intact red cells by ektacytometry, if heat-treated, 4) two peptides of membrane protein 4.2 were detected in a trace amount by Western blot. Five phenotypes were categorized by Western blot, as based on the type of membrane protein 4.2 present; 1) 72 kDa peptide alone, 2) 72 kDa + 74 kDa in a trace amount, 3) 72 kDa + 74 kDa both in a trace amount, 4) 72 kDa + 68 kDa in a trace amount, and 5) complete deficiency.