Common<unk>  A number of genes have been linked to common<unk>  (many involve the same gene as forms of Hereditary spherocytosis, or HS): Type OMIM Gene EL1 or HS5 EPB41 EL2 or HS3 SPTA1 EL3 or HS2 SPTB EL4 or HS4 or SEO SLC4A1 These mutations have a common end result; they destabilise the cytoskeletal scaffold of cells. This stability is especially important in erythrocytes as they are constantly under the influence of deforming shear forces. As disc-shaped erythrocytes pass through capillaries, which can be 2-3 micrometres wide, they are forced to assume an elliptical shape in order to fit through. Normally, this deformation lasts only as long as a cell is present in a capillary, but in<unk>  the instability of the cytoskeleton means that erythrocytes deformed by passing through a capillary are forever rendered elliptical. These elliptical cells are taken up by the spleen and removed from circulation when they are younger than they would normally be, meaning that the erythrocytes of people with<unk>  have a shorter than average life-span (a normal person's erythrocytes average 120 days or more).Figure 2 - A schematic diagram representing the relationships between cytoskeletal molecules as relevant to<unk> . * EL2 and EL3: The most common genetic defects (present in two-thirds of all cases of<unk>  are in genes for the polypeptides α-spectrin or β-spectrin. These two polypeptides combine with one another in vivo to form an αβ heterodimer. These αβ heterodimers then combine to form spectrin tetramers. These spectrin tetramers are among the basic structural subunits of the cytoskeleton of all cells in the body. Although there is much interindividual variability, it is generally true that α-spectrin mutations result in an inability of α-spectrin to interact properly with β-spectrin to form a heterodimer. In contrast, it is generally true that β-spectrin mutations lead to αβ heterodimers being incapable of combining to form spectrin tetramers. In both cases the end result is a weakness in the cytoskeleton of the cell. Individuals with a single mutation in one of the spectrin genes are usually asymptomatic, but those who are homozygotes or are compound heterozygotes (i.e. they are heterozygous for two different<unk> -causing mutations) have sufficient cell membrane instability to have a clinically significant haemolytic anaemia. * EL1: Less common than spectrin mutations are band 4.1 mutations. Spectrin tetramers must bind to actin in order to create a proper cytoskeleton scaffold, and band 4.1 is an important protein involved in the stabilisation of the link between spectrin and actin. Similarly to the spectrin mutations, band 4.1 mutations cause a mild haemolytic anaemia in the heterozygous state, and a severe haemolytic disease in the homozygous state. * EL4: Southeast Asian ovalocytosis is associated with the Band 3 protein. * Another group of mutations that lead to<unk>  are those that cause glycophorin C deficiencies. There are three phenotypes caused by abnormal glycophorin C, these are named Gerbich, Yus and Leach (see glycophorin C for more information). Only the rarest of the three, the Leach phenotype, causes<unk> . Glycophorin C has the function of holding band 4.1 to the cell membrane. It is thought that<unk>  in glycophorin C deficiency is actually the consequence of a band 4.1 deficit, as glycophorin C deficient individuals also have reduced intracellular band 4.1 (probably due to the reduced number of binding sites for band 4.1 in the absence of glycoprotein C). Inheritance of multiple mutations tends to infer more serious disease. For instance, the most common genotype responsible for HPP occurs when the affected individual inherits an α-spectrin mutation from one parent (i.e. one parent has<unk>  and the other parent passes on an as-yet-undefined defect that causes the affected individual's cells to preferentially produce the defective α-spectrin rather than normal α-spectrin.
Hereditary elliptocytosis
Diamond–Blackfan anemia
Hereditary spherocytosis
Thiamine responsive megaloblastic anemia syndrome
Myomatous erythrocytosis syndrome
Refractory anemia with excess of blasts
Refractory anemia with ring sideroblasts
Macroglobulinemia