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| MUTATION | |
IVS-I (-1) or codon 30 (G->C); AG^GTTGGT->AC^GTTGGT | |
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| AMINO ACID REPLACEMENT | |
Position 30 AGG->ACG (Arg->Thr; Hb Monroe) | |
| TYPE OF BETA-THAL | |
beta° | |
| MECHANISM | |
The G->C change in the AG dinucleotide, which is required for normal splicing and is part of codon 30 (the first two nts of the AGG codon), will prevent splicing completely and no normal mRNA is formed | |
| IDENTIFICATION | |
Amplification of the beta-globin gene; DNA sequencing; dot-blot analysis with allele specific probes; ASO | |
| HEMATOLOGY IN HETEROZYGOTE(S) | |
Hb 11.3 g/dl; MCV 56 fl; MCH 18.5 pg; Hb A2 4.4%; Hb F 1.0% | |
| HEMATOLOGY IN HOMOZYGOTE(S) | |
Transfusion-dependent beta-thal major (Refs. 3,4,5) | |
| OCCURRENCE | |
In a Black family, a few Tunisian, Indian, and United Arab Emirate families | |
| HAPLOTYPE | |
[- - + + - + + + +] | |
| FOUND IN COMBINATION WITH ABNORMAL HB(S) | |
None reported | |
| FOUND IN COMBINATION WITH BETA-THAL ALLELE(S) | |
The proband was a compound heterozygote: -29 (A->G)/IVS-I-1(-1) (G->C); Hb 8.6 g/dl; MCV 80 fl; MCH 25.6 pg; Hb A2 3.6%; Hb F 16.5%; patient was quite often transfused | |
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TABLE A. Transfusion Requirements of Patients Homozygous or Compound Heterozygous for Hb Monroe (from the United Arab Emirates; Ref. 6)
| Sex-Age | Other Chromosome | Alpha Gene Status | First Transfusion
(in months) |
| F-8 | Homozygous | alphaalpha/alphaalpha | 30 |
| F-9 | -101, C->T | alphaalpha/alphaalpha | None |
| F-18 | IVS-I-110, G->A | alphaalpha/alphaalpha | 30 |
| F-4 | IVS-I-110, G->A | alphaalpha/alphaalpha | 64 |
| F-10 | IVS-I-110, G->A | -alpha(-3.7)/alphaalpha | 46 |
| F-12 | Cd 22, -AAGTTGG | alphaalpha/alphaalpha | 12 |
| M-11 | Cd 22, -AAGTTGG | alphaalpha/alphaalpha | 6 |
| F-11 | IVS-I-5, G->C | alphaalpha/alphaalpha | 5 |
| F-7 | 619 bp deletion | -alpha(-3.7)/alphaalpha | 17 |
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| OTHER INFORMATION | |
Several attempts have been made to isolate Hb Monroe with questionable results; none should be present. The IVS-I (-1) G->C change for the homozygous patient described in Ref. 4 is linked to a C->G mutation at position -42 of the beta-globin gene promoter | |
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| REFERENCES |
| 1. | |
Gonzalez-Redondo, J.M., Stoming, T.A., Kutlar, F., Kutlar, A., Hu, H., Wilson, J.B., and Huisman, T.H.J.: Hemoglobin, 13:67, 1989. | |
| 2. | |
Chibani, J., Vidaud, M., Duquesnoy, P., Bergé-Lefranc, J.L., Pirastu, M., Ellouze, F., Rosa, J., and Goossens, M.: Hum. Genet., 78:190, 1988. | |
| 3. | |
Fattoum, S., Guemira, F., Öner, C, Öner R., Li, H-W., Kutlar, F., and Huisman, T.H.J.: Hemoglobin, 15:11, 1991. | |
| 4. | |
Fedorov, A.N., Nasyrova, F.Yu., Smirnova, E.A., Bocharova, T.N., and Limborska, S.A.: Hemoglobin, 17:275, 1993. | |
| 5. | |
Gupta, R.B., Tiwary, R.S., Pande, P.L., Kutlar, F., Öner C., Öner, R., and Huisman, T.H.J.: Hemoglobin, 15:441, 1991. | |
| 6. | |
El-Kalla, S. and Mathews, A.R.: Hemoglobin, 21:237, 1997. | |