Disease relevance of Elliptocytosis, Hereditary

• Mutations affecting the conversion of spectrin dimers to tetramers result in hereditary elliptocytosis (HE), whereas a deficiency of human erythroid alpha- or beta-spectrin results in hereditary spherocytosis (HS) [1].
• Mutations in 4.1R can cause hereditary elliptocytosis, a disease characterized by a loss of the normal discoid morphology of erythrocytes, resulting in hemolytic anemia [1] [2].
• Hereditary spherocytosis, hereditary elliptocytosis or poikilocytosis, Southeast Asian ovalocytosis are hereditary hemolytic anemias, due to mutations in the genes encoding ankyrin, the anion exchanger, spectrin, protein 4.1 or protein 4.2, which are main proteins of the membrane [3].
• Hemoglobinopathies, G6PD deficiency, and hereditary elliptocytosis in Bahrain [4].

High impact information on Elliptocytosis, Hereditary

• Molecular basis of hereditary elliptocytosis due to protein 4.1 deficiency [5].
• We here analyze the molecular basis of heterozygous 4.1(-) hereditary elliptocytosis, associated with protein 4.1 partial deficiency, in nine related French families. cDNA sequencing revealed a single codon deletion (AAA) resulting in a lysine residue deletion within the 10-kD binding domain, 3' of Motif I [6].
• alpha I/74 hereditary elliptocytosis (HE) is a subgroup of HE in which patients exhibit an impaired self-association of spectrin dimers and an abnormal proteolytic cleavage of the alpha I domain of spectrin [7].
• To explain the transient anemia and poikilocytosis seen during infancy in hereditary elliptocytosis (HE), we resealed erythrocyte (RBC) ghosts from affected children or their elliptocytic parents with 2,3-diphosphoglycerate (DPG) (0-8 mM), a compound that dissociates membrane skeletons, then measured ghost mechanical stability in the ektacytometer [8].
• Defective binding of spectrin to ankyrin in a kindred with recessively inherited hereditary elliptocytosis [9].

Chemical compound and disease context of Elliptocytosis, Hereditary

• Membrane skeletons, produced from ghosts of both types of hereditary elliptocytosis by Triton X-100 extraction, were unstable when mechanically shaken [10].
• Effect of brilliant cresyl blue on erythrocytes in hereditary elliptocytosis [11].
• Alpha-thalassaemia, increased synthesis of Hb F, and glucose-6-phosphate deficiency may ameliorate the clinical condition at phenotype level, and the co-inheritance of hereditary ovalocytosis aggravates it [12].

Biological context of Elliptocytosis, Hereditary

• Heterozygous 4.1(-) hereditary elliptocytosis results from the absence of one haploid set of protein 4.1, a major component of the red cell skeleton [13].

Anatomical context of Elliptocytosis, Hereditary

• Erythrocyte membranes (ghosts) and membrane skeletons (submembranous reticula of spectrin, actin, and protein 4.1 prepared by extracting ghosts with Triton X-100) from 15 patients with hereditary elliptocytosis (HE) were elliptical, which indicates that the primary defect responsible for the abnormal shape of these cells resides in the skeleton [14].
• Biochemical studies on red blood cell membrane cytoskeleton showed that beta-spectrin, alpha-spectrin and protein 4.1, which are usually altered in hereditary elliptocytosis (HE), were normal in our cases [15].

Gene context of Elliptocytosis, Hereditary

• Mild spherocytic hereditary elliptocytosis and altered levels of alpha- and gamma-adducins in beta-adducin-deficient mice [16].
• The mutations responsible for hereditary elliptocytosis (HE) and its aggravated form, poikilocytosis (HP), lie in the SPTA1 and SPTB gene, already mentioned, and in the EPB41 gene encoding protein 4 [17].
• The preceding companion paper presents a biochemical study of two abnormal protein 4.1 species from individuals with the red blood cell disorder, hereditary elliptocytosis [18].
• We used naturally mutated red blood cells (RBCs) with primary genetic defects resulting in the absence of protein 4.1 (4.1[-] hereditary elliptocytosis) or glycophorin C (Leach elliptocytosis) [19].
• It results in the aggravated expression of hereditary elliptocytosis due to SPTA1 gene mutations occurring in trans [20].

References