In several large surveys a few typical beta-thal alleles cannot be explained by any mutation in the beta-globin gene or by deletion, detectable by a gene mapping procedure. It has been suggested that the defect might be the result of a mutation in the locus control region (LCR) of the beta-globin gene which is located some 40 kb 5' to the epsilon-globin gene; deletions involving this controlling region, but with an intact beta-globin gene, inactivate the beta-globin gene and cause beta-thal. Such an anomaly lies in cis to the beta-globin gene and the two abnormalities (LCR variation and beta°-thal) do not segregate.
Thein et al (1) recently reported a beta-thal condition in an English family which did segregate of the beta-globin gene cluster. Linkage analysis with RLFP methodology clearly identified this segregation. It might well be that this novel type of beta-thal is due to a mutation in one of the many genes producing a protein factor which can affect the activity of the beta-globin gene. Additional cases in families from Italy, Cyprus, and from Holland have been presented (2-4).
|1.||Thein, S.L., Wood, W.G., Wickramasinghe, S.N., and Galvin, M.C.: Blood, 82:961, 1993.|
|2.||Murru, S., Loudianos, G., Porcu, S., Sciarratta, G.V., Agosti, S., Parodi, M.I., Cao, A., and Pirastu, M.: Br. J. Haematol., 81:283, 1992.|
|3.||Drousiotou, A., Christopoulos, G., Kleanthous, M., Kyriacou, K., Pavlou, E., Kyrri, A., Kalogirou, E., Vassiliades, Ph., Kouspou, Y., Angastiniotis, M., and Ioannou, P.: Abstract 154, 6th International Conference on Thalassaemia and the Haemoglobinopathies, Malta, April 1997.|
|4.||Giordano, P.C., Harteveld, C.L., Haak, H.L., Batelaan, D., van Delft, P., Plug, R.J., Smilevska, D., and Bernini, L.F.: Abstract 19, 6th International Conference on Thalassaemia and the Haemoglobinopathies, Malta, April 1997.|