TYPE Canadian (epsilongammadeltabeta)°-Thal (see Fig. 17)
CAUSE A large deletion removing all the functional genes and the psibeta gene in the beta-globin gene cluster. The minimal size of the deletion is ~185 kb. The 5' breakpoint is 5' to the TaqI restriction site or more than 59 kb 5' to the epsilon gene, while the 3' end is located beyond the BglII site, 82 kb 3' to the beta gene.
DETECTION The data obtained from the restriction endonuclease mapping for the Canadian deletion is the same as for the Croatian (epsilongammadeltabeta)°-thal except for the gammabeta1 probe which did not produce an abnormal fragment in the affected individuals, thus indicating that the 5' end of the deletion is 5' to the TaqI restriction site, ~59 kb 5' to the beta gene.
PHENOTYPE The proband, a newborn baby, had moderate anemia at birth, low MCV (85 fl), high erythroblast count and reticulocytes. A large number of target cells associated with microcytosis were evident in the blood smear. The microcytosis and hypochromia worsened soon after birth. Improvement in the baby's condition began after 3 months of age when the Hb F level had fallen to 40%. The father and at least 10 additional family members had a distinct anemia with severe microcytosis and hypochromia. Hb F and Hb A2 levels in the affected individuals were normal and Ggamma values were in the normal range. The hematology of the heterozygotes was not different from the other types of (epsilongammadeltabeta)°-thal.
DISTRIBUTION Found in a large Canadian family.
NOTE A similar deletion has been observed in a Dutch patient; it was a de novo occurrence because both parents were normal. This deletion cannot be distinguished from the Canadian (epsilongammadeltabeta)°-thal with gene mapping data only.
1. Diaz-Chico, J.C., Huang, H.J., Juricic, D., Efremov, G.D., Wadsworth, L.D., and Huisman, T.H.J.: Acta Haematol., 80:79, 1988.
2. Abels, J., Michiels, J.J., Giordano, P.C., Bernini, L.F., Baysal, E., Smetanina, N.S., Kazanetz, E.G., Leonova, J.Y., and Huisman, T.H.J.: Acta Haematol., 96:108, 1996.

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.