I-e. Beta-Thalassemia Unlinked to a Beta-Globin Gene Mutation or Deletion

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).

REFERENCES

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.


REFERENCES
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.

This material is from the book A Syllabus of Thalassemia Mutations (1997) by Titus H.J. Huisman, Marianne F.H. Carver, and Erol Baysal, published by The Sickle Cell Anemia Foundation in Augusta, GA, USA. Copyright © 1997 by Titus H.J. Huisman. All rights reserved. Neither this work nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, microfilming and recording, or by any information storage and retrieval systems, without permission in writing from the Author.