MUTATION IVS-I-6 (T->C); the Portuguese type
 
AMINO ACID REPLACEMENT None
TYPE OF BETA-THAL beta+
MECHANISM This T->C mutation at nt 6 of IVS-I reduces the efficiency of splicing at the 5' site (see scheme)
Codon #          30   IVS-I             
Normal AG^ GTTGGTATCAAGGTT
IVS-I-6 (T->C) AG^ GTTGGCATCAAGGTT
IDENTIFICATION Amplification or cloning of the beta-globin gene; DNA sequencing; amplification or dot-blot analysis with allele specific primers or probes; gene mapping with SfaNI; ASO
HEMATOLOGY IN HETEROZYGOTE(S) From Ref. 6 (n=33): Hb 11.95±2.4 g/dl; MCV 71.0±6.3 fl; MCH 22.3±1.7 pg; Hb A2 3.9±0.55%; Hb F 1.15± 1.05%
HEMATOLOGY IN HOMOZYGOTE(S) Thalassemia intermedia; see table overleaf
OCCURRENCE One of the most common alleles in (the western part) of the Mediterranean Basin; see Tables III, IV, VII, VIII, IX, and X
HAPLOTYPE VI [- - + + - - - +] or VII [+ - - - - - - +]
FOUND IN COMBINATION WITH ABNORMAL HB(S) Hb S; Hb C; Hb Valletta [beta87(F3)Thr->Pro]
FOUND IN COMBINATION WITH BETA-THAL ALLELE(S) Many alleles
OTHER INFORMATION None

TABLE A. Hematological and Hb Composition Data for 29 Untransfused IVS-I-6 (T->C) Homozygotes (Ref. 5) (country of origin: P = Portugal; I = Italy; T = Turkey; M = Macedonia)
Origin-Case Sex-Age RBC 1012/l Hb g/dl PCV l/l MCV fl MCH pg MCHC g/dl A2 % F %
P-L.R. M-14 3.94 7.6 0.255 64.7 19.3 29.8 4.5 35.4
P-M.S. F-24 4.26 8.2 0.275 64.6 19.2 29.8 4.9 24.6
P-F.R.I M-28 4.87 8.6 0.284 58.3 17.7 30.3 6.4 11.4
P-F.R.II M-23 5.22 9.7 0.315 60.3 18.6 30.8 5.6 20.8
P-C.L. F-19 3.07 6.7 0.262 85.3 21.8 25.6 6.3 16.2
P-V.R. F-38 3.29 6.8 0.282 85.7 20.7 24.1 7.1 11.0
P-H.B. M-10 3.58 7.0 0.252 70.4 19.6 27.8 6.6 13.6
P-H.S.II M-43 4.83 8.6 0.331 68.5 17.8 26.0 7.7 9.2
P-O.R. M-42 4.80 8.0 0.268 55.8 16.7 29.9 6.5 7.4
P-M.H. F-32 5.41 8.8 0.293 54.6 16.3 30.0 7.3 4.8
P-M.A. F-58 4.08 6.2 0.290 71.1 15.2 21.4 8.0 2.4
P-S.B. M-26 4.71 7.8 0.300 63.7 16.6 26.0 8.8 2.9
P-P.S. F-36 4.69 8.5 0.303 64.6 18.1 28.1 5.2 21.5
I-464 F-11 4.73 8.0 0.287 60.7 16.9 27.9 5.2 24.7
I-375 F-2 4.95 7.6 0.274 55.4 15.4 27.7 5.8 12.1
I-386 M-19 4.15 7.3 0.281 67.7 17.6 26.0 6.7 18.1
I-242 F-8 3.70 6.6 0.253 68.4 17.8 26.1 5.6 9.6
I-385 M-4 3.62 6.6 0.249 67.5 17.9 26.5 6.4 6.8
I-376 F-12 5.50 7.8 0.279 50.7 14.2 28.0 7.7 2.0
I-380 F-13 4.01 7.7 0.292 72.8 19.3 26.4 6.5 15.9
T-74 F-9 5.19 8.2 0.303 58.4 15.8 27.1 8.0 5.2
T-686 M-21 2.77 5.0 0.217 78.3 18.1 23.0 8.8 6.4
T-687 F-15 2.94 5.5 0.235 79.9 18.7 23.4 8.1 5.8
T-688 M-42 4.83 9.6 0.309 64.0 19.9 31.1 7.6 2.5
T-689 M-46 3.16 6.9 0.254 80.4 21.8 27.2 8.8 5.3
T-690 M-18 4.33 7.1 0.245 56.6 16.4 29.0 8.6 5.7
T-692 F-9 5.22 8.5 0.293 56.1 16.3 29.0 8.7 6.2
M-P-01 F-37 4.23 7.3 0.315 74.5 17.3 25.2 8.5 6.0
M-P-01B M-31 5.45 9.9 0.388 71.2 18.2 25.5 6.2 19.2
       
REFERENCES
1. Tamagnini, G.P., Lopez, M.C., Castanheira, M.E., Wainscoat, J.S., and Wood, W.G.: Br. J. Haematol., 53:189, 1983.
2. Orkin, S.H., Kazazian, H.H., Jr., Antonarakis, S.E., Goff, S.C., Boehm, C.D., Sexton, J.P., Waber, P.G., and Giardina, P.J.V.: Nature, 296:627, 1982.
3. Scerri, C.A., Abela, W., Galdies, R., Pizzuto, M., Grech, J.L., and Felice, A.E.: Br. J. Haematol., 83: 669, 1993.
4. Tamagnini, G.P., Gonçalves, P., Ribeiro, M.L.S., Kaeda, J., Kutlar, F., Baysal, E., and Huisman, T.H.J.: Hemoglobin, 17:31, 1993.
5. Efremov, D.G., Dimovski, A.J., Baysal, E., Ye, Z., Adekile, A.D., Ribeiro, M.L.S., Schiliro, G., Altay, Ç., Gürgey, A., Efremov, G.D., and Huisman, T.H.J.: Br. J. Haematol., 86:824, 1994.
6. Öner, R., Altay, Ç., Gurgey, A., Aksoy, M., Kilinç, Y., Stoming, T.A., Reese, A.L., Kutlar, A., Kutlar, F., and Huisman, T.H.J.: Hemoglobin, 14:1, 1990.


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.