TYPE Spanish (deltabeta)°-Thal (see Fig. 14)
 
CAUSE A large deletion of ~115 kb extending from the midpoint between the psibeta and delta genes to ~100 kb 3' to the beta gene. The 3' breakpoint extends beyond that of any other similar deletion. The Spanish (deltabeta)°-thal removes ~11 and 17 kb more DNA at the 3' end than the Black HPFH-1 and HPFH-2, respectively. The 5' end is within several hundred nts of the 5' breakpoints of the Black HPFH-1 and the Italian HPFH-4, and maps into the inverted Alu I repeat.
DETECTION Gene mapping with different enzymes and probes. The 3' breakpoint was determined through molecular cloning of a unique DNA fragment from the 3' end.
PHENOTYPE Homozygous patients show a mild-to-moderate chronic hemolytic anemia, morphological changes typical of thalassemia, and 100% Hb F in their peripheral blood. The levels of the AgammaT and Ggamma chains are approximately equal; the chromosomes with the deltabeta-thal deletion carries the ATA->ACA mutation at codon 75 (Ile->Thr; Agamma). Heterozygotes exhibit typical thalassemic RBC morphology; hypochromia (MCH 20-26 pg), microcytosis (MCV 63-77 fl), uneven distribution of Hb F (5-13%), Hb A2 (1.3-2.7%). Hb F consists of 30-45% Ggamma and exclusively of AgammaT chains produced by the AgammaT gene in cis.
DISTRIBUTION Spanish (deltabeta)°-thal was first reported in 10 homozygous patients in six families from Spain. The deletion appears to be rather common.
       
REFERENCES
1. Ottolenghi, S., Giglioni, B., Taramelli, R., Comi, P., Mazza, U., Saglio, G., Camaschella, C., Izzo, P., Cao, A., Galanello, R., Gimferrer, E., Baiget, M., and Gianni, A.M.: Pro. Natl. Acad. Sci. USA, 79:2347, 1982.
2. Ottolenghi, S. and Giglioni, B.: Nature, 300:700, 1982.
3. Baiget, M., Gimferrer, E., Fernandez, I., Romero, C., Mira, Y., Perez, M.L., and Miguel, A.: Acta Haematol., 70:341, 1983.
4. Camaschella, C., Serra, A., Saglio, G., Baiget, M., Malgaretti, N., Mantovani, R., and Ottolenghi, S.: Blood, 70:593, 1987.

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.