Ankyrin deficiency

Ankyrin deficiency, amounting to a reduction of approximately 50%, has been found in some patients with the dominant type of HS. A primary defect in ankyrin almost certainly reduces the assembly of spectrin into the membrane skeleton of the red blood cell (Davies and Lux, 1989). 

The primary biochemical defects of HS are linked to proteins important to the interaction between the membrane skeleton and the lipid bilayer involving a- and /3-spectrin, ankyrin, band 3, and protein 4.2 (Gallagher and Forget, 1998). Combined spectrin and ankyrin deficiency (Coetzer et al, 1988 Pekrun et al, 1993 Sawides et al., 1993) is most commonly observed, followed by band 3 deficiency (Iolascon et al, 1992 Jarolim et al,... 

Sawides, P., Shalev, O., John, K. M., and Lux, S. E. (1993). Combined spectrin and ankyrin deficiency is common in autosomal dominant hereditary spherocytosis. Blood 82, 2953-2960. 

Hereditary spherocytosis Deficiencies in the amount or in the structure of a or p spectrin, ankyrin, band 3 or band 4.1... 

One cause of hereditary spherocytosis (Figure 52-5) is a deficiency in the amount of spectrin or abnormalities of its structure, so that it no longer tightly binds the other proteins with which it normally interacts. This weakens the membrane and leads to the spherocytic shape. Abnormalities of ankyrin and of bands 3 and 4.1 are involved in other cases. 

Although much of the focus has been on the DPC of striated muscle, it is likely that desmin attachments to dense plaques of smooth muscle play critical roles in regulating the transmission of contractile forces in this tissue as well. This is particularly relevant in light of the observed defects in smooth muscle of desmin-deficient mice, in which active force per cross-sectional area was reduced to 40% of controls of smooth muscle tissue (Sjuve et al, 1998). IFAP candidates for serving this linking function are plectin and other components of the actin-rich cortex, including calponin (which also plays a role in the cytoplasm of smooth muscle cell dense bodies see below), and the spectrin/ankyrin complex. 

Hassoun, H., Vassiliadis, J. N., Murray, J., Yi, S. J., Hanspal, M., Ware, R. E., Winter, S. S., Chiou, S. S., and Palek, J. (1995). Molecular basis of spectrin deficiency in beta spectrin Durham. A deletion within beta spectrin adjacent to the ankyrin-binding site precludes spectrin attachment to the membrane in hereditary spherocytosis. / Clin. Invest. 96, 2623-2629. 

Pekrun, A., Eber, S. W., Kuhlmey, A., and Schroter, W. (1993). Combined ankyrin and spectrin deficiency in hereditary spherocytosis. Ann. Hematol. 67, 89-93. 

Rybicki, A. C., Heath, R., Wolf, J. L., Lubin, B., and Schwartz, R. S. (1988). Deficiency of protein 4.2 in erythrocytes from a patient with a Coombs negative hemolytic anemia. Evidence for a role of protein 4.2 in stabilizing ankyrin on the membrane. 

It is now clear that a deficiency or dysfunction of ankyrin, the protein that anchors the spectrin-based skeleton to band 3 (Fig. 6-3), may represent a common membrane lesion in HS. The synthesis of ankyrin and its assembly on the membrane were reduced, and as a consequence, assembly of spectrin was also impaired despite normal spectrin synthesis. In 1996,Jarolim et al. showed that a deficiency of ankyrin (and its related spectrins) was present in 60% of 166 unrelated patients with HS. 

A deficiency of protein 4.2 has also been noted in several patients with recessively inherited HS, particularly in the Japanese population. Although the physiological role of protein 4.2 remains to be established, this protein is thought to stabilize the binding of band 3 to spectrin mediated by ankyrin. 

Ankyrin 8 Ankyrin and spectrin deficiency Ankyrin gene deletion Promoter region mutations Ankyrin Stuttgart (329 2-nt deletion) Ankyrin Einbeck (572 1-nt Insertion) Ankyrin Marburg (797/798 4-nt deletion) Ankyrin Bovenden (1436Arg—Her) Others AD orAR Mild to severe 50%-60%... 

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