MUTATION		Codon 121 (G->T); GAA(Glu)->TAA(stop codon)
AMINO ACID REPLACEMENT		None
TYPE OF BETA-THAL		beta° (dominant beta-thal trait)
MECHANISM		The G->T mutation changes codon 121 into a stop codon; the shortened beta chain (120 residues) is likely rapidly catabolized causing this TYPE OF BETA-THAL
IDENTIFICATION		Amplification of the beta-globin gene; sequencing of amplified DNA; dot-blot analysis with allele specific probes
HEMATOLOGY IN HETEROZYGOTE(S)		Moderately severe beta-thal trait with inclusion bodies upon incubation with dye; reticulocytosis; increased Hb A2 and Hb F; splenomegaly; splenectomy; considerable variation in phenotype; Hb 9.0-10.0 g/dl; MCV 60-65 fl; MCH 18-22 pg
HEMATOLOGY IN HOMOZYGOTE(S)		None observed
OCCURRENCE		First observed as a de novo mutation in a Greek-Cypriot-Polish child (1); in a Swiss (2,3); in British families (4); in Czech families (5); in Japanese families (6,7); in a Dutch family (8)
HAPLOTYPE		Not reported
FOUND IN COMBINATION WITH ABNORMAL HB(S)		None
FOUND IN COMBINATION WITH BETA-THAL ALLELE(S)		None
OTHER INFORMATION		Attempts to isolate the shortened betaX chain were partially successful (0.05-0.1% of total Hb) (Ref. 9)

REFERENCES
1.		Kazazian, H.H., Jr., Orkin, S.H., Boehm, C.D., Goff, S.C., Wong, C., Dowling, C.E., Newburger, P.E., Knowlton, R.G., Brown, V., and Donis-Keller, H.: Am. J. Hum. Genet., 38:860, 1986.
2.		Fei, Y.J., Stoming, T.A., Kutlar, A., Huisman, T.H.J., and Stamatoyannopoulos, G.: Blood, 73:1075, 1989.
3.		Stamatoyannopoulos, G., Woodson, R., Papayannopoulou, Th., Heywood, D., and Kurachi, S.: N. Engl. J. Med., 290:939, 1974.
4.		Thein, S.L., Hesketh, C., Taylor, P., Temperley, I.J., Hutchinson, R.M., Old, J.M., Wood, W.G., Clegg, J.B., and Weatherall, D.J.: Proc. Natl. Acad. Sci. USA, 87;3924, 1990.
5.		Indrak, K., Brabec, V., Indrakova, J., Chrobak, L., Sakalova, A., Jarosova, M., Cermak, J., Fei, Y-J., Kutlar, F., Gu, Y-C., Baysal, E., and Huisman, T.H.J.: Hum. Genet., 88:399, 1992.
6.		Naritomi, Y., Naito, Y., Nakashima, H., Yokota, E., and Imamura, T.: Hum. Genet., 80:11, 1988.
7.		Yamamoto, Ku., Yamamoto, Ki., Hattori, Y., Yamashiro, Y., Hoshitani, M., Morishita, M., Ohba, Y., Katahira, H., Karasawa, , M., Omine, M., Narukiyo, T., Hirabayashi, K., and Miyawaki, S.: Hemoglobin, 16:295, 1992.
8.		Giordano, P.C., Harteveld, C.L., Michiels, J.J., Schelfhout, L.j., Batelaan, D., van Delft, P., Plug, R.J., and Bernini, L.F.: Abstract 20, 6th International Conference on Thalassaemia and the Haemoglobinopathies, Malta, April 1997.
9.		Adams, J.G., III, Morrison, W.T., Steinberg, M.H., Kazazian, H.H., Jr., and Orkin, S.H.: Abstract 155, Blood, 64:69a (Suppl. 1), 1986.

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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.