MUTATION Codon 126 (T->G); GTG(Val)->GGG(Gly)
AMINO ACID REPLACEMENT Val->Gly (Hb Neapolis or Hb Dhonburi)
TYPE OF BETA-THAL Mild beta-thal trait
MECHANISM The mutation results in the synthesis of a mildly unstable betaX chain which may be removed quite quickly from circulation by proteolysis causing a thalassemic condition
IDENTIFICATION Amplification of the beta-globin gene; DNA sequencing; allele specific oligonucleotide hybridization
HEMATOLOGY IN HETEROZYGOTE(S) Nearly normal hematology except a mild microcytosis and hypochromia (MCV 75-82 fl; MCH 24-27 pg); Hb A2 marginally increased; mild reticulocytosis
OCCURRENCE In a few Italian, Thai, and German families; highest incidence in Campania (Southern Italy) (Ref. 4)
HAPLOTYPE V [+ O - - - - + -]
FOUND IN COMBINATION WITH ABNORMAL HB(S) In combination with Hb Lepore (Ref. 3): Hb 10.2 g/dl; MCV 61.2 fl; MCH 19.9 pg; Hb A2 3.7%; (age 14 months)
FOUND IN COMBINATION WITH BETA-THAL ALLELE(S) Causes a beta-thal intermedia; a German child was compound heterozygote for the codon 126 (T->G) and the IVS-I-5 (G->C) mutations
OTHER INFORMATION The betaX chain can be detected by reversed phase HPLC (about 30% of total beta in the heterozygote); unstable
1. Pagano, L., Lacerra, G., Camardella, L., De Angioletti, M., Fioretti, G., Maglione, G., de Bonis, C., Guarino, E., Viola, A., Cutolo, R., De Rosa, L., and Carestia, C.: Blood, 78:3070, 1991.
2. Divoky, V., Bissé, E., Wilson, J.B., Gu, L-H., Wieland, H., Heinrichs, I., Prior, J.F., and Huisman, T.H.J.: Biochim. Biophys. Acta, 1180:173, 1992.
3. Pagano, L., Carbone, V., Fioretti, G., Viola, A., Buffardi, S., Rametta, V., Desicato, S., Pucci, P., and De Rosa, C.: Hemoglobin, 21:1, 1997.
4. Pagano, L., Fioretti, G., Viola, A., Carbone, V., Rametta, V., Buffardi, S., Filosa, A., Saviano, A., Pucci, P., and De Rosa, C.: Abstract 107, 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.