| MUTATION | Codon 39 (C->T); CAG(Gln)->TAG(stop codon) | ||
|---|---|---|---|
| AMINO ACID REPLACEMENT | None | ||
| TYPE OF BETA-THAL | beta° | ||
| MECHANISM | This mutation changes codon 39 into a stop codon terminating translation | ||
| IDENTIFICATION | Cloning of the beta-globin gene; amplification of the beta-globin gene and sequencing; dot-blot analysis; ARMS; gene mapping with MaeI | ||
| HEMATOLOGY IN HETEROZYGOTE(S) | Typical for beta°-thal with low MCV and MCH values; microcytosis; hypochromia (n=10): Hb 11.1±1.35 g/dl; MCV 72.6±8.5 fl; MCH 20.2±1.1 pg; Hb A2 4.85±0.5%; Hb F 1.25±1.0% (Ref. 4) | ||
| HEMATOLOGY IN HOMOZYGOTE(S) | Severe transfusion-dependent beta-thal | ||
| OCCURRENCE | One of the major beta-thal alleles in the Mediterranean area; see Tables III through X for frequency data | ||
| HAPLOTYPE | Types I; II; IX | ||
| FOUND IN COMBINATION WITH ABNORMAL HB(S) | With Hb S, Hb C, Hb E, causing moderately severe thalassemia intermedia (and sickling) | ||
| FOUND IN COMBINATION WITH BETA-THAL ALLELE(S) | With numerous beta° or beta+ alleles; in most instances, the compound heterozygotes are transfusion-dependent | ||
| OTHER INFORMATION | The beta°-thal codon 39 mutation can also be detected by enzymatic digestion with MaeI (Ref. 3) |
| REFERENCES | |||
| 1. | Orkin, S.H. and Goff, S.C.: J. Biol. Chem., 256:9782, 1981. | ||
| 2. | Trecartin, R.F., Liebhaber, S.A., Chang, J.C., Lee, K.Y., and Kan, Y.W.: J. Clin. Invest., 68:1012, 1981. | ||
| 3. | Thein, S.L., Wainscoat, J.S., Lynch, J.R., Weatherall, D.J., Sampietro, M., and Fiorelli, G.: The Lancet, i:1095, 1985. | ||
| 4. | 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. | ||