Hereditary haemolytic anaemias: unexpected sequelae of mutations in the genes for erythroid membrane skeletal proteins.
Ankyrins, Blood-Proteins, Calmodulin-Binding-Proteins, Cholelithiasis, Cytoskeletal-Proteins, Cytoskeleton, Erythrocytes, Leukocytosis, Membrane-Proteins, Microtubule-Associated-Proteins, Research-Support-U, S, -Gov't-P, H, S, Spectrin, Splenomegaly, Thrombosis
J Pathol 2004 Nov; 204(4):450-9.
Although the haemolytic anaemia may be the primary concern for hereditary spherocytosis and elliptocytosis patients, it is clear that their situation can be compromised by primary and secondary defects in erythroid and non-erythroid systems of the body. All seven of the red cell membrane skeletal proteins discussed in this review are also expressed in non-erythroid tissues, and mutations in their genes have the potential to cause non-erythroid defects. In some instances, such as the protein 4.1R and ANK1 neurological deficits, the diagnosis is clear. In other instances, because of the complex expression patterns involved, the non-erythroid effects may be difficult to assess. An example is the large multidomain, multifunctional band 3 protein. In this case, the location of the mutation can cause defects in one functional domain or isoform and not the other. In other cases, such as the beta-adducin null mutation, other isoforms may partially compensate for the primary deficiency. In such cases, it may be that the effects of the deficit are subtle but could increase under stress or with age. To be completely successful, treatment strategies must address both primary and secondary effects of the anaemia. If gene replacement therapy is to be used, the more that is known about the underlying genetic mechanisms producing the multiple isoforms the better we will be able to design the best replacement gene. The various animal models that are now available should be invaluable in this regard. They continue to contribute to our understanding of both the primary and the secondary effects and their treatment.
Birkenmeier, C S. and Barker, J E., "Hereditary haemolytic anaemias: unexpected sequelae of mutations in the genes for erythroid membrane skeletal proteins." (2004). Faculty Research 2000 - 2009. 944.