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MUTATION | |
IVS-I-6 (T->C); the Portuguese type | |
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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) | |
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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 | |
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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 | | |
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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. | |