| MUTATION | Codon 114 (T->C); CTG(Leu)->CCG(Pro) | ||
|---|---|---|---|
| AMINO ACID REPLACEMENT | Leu->Pro (Hb Durham-N.C. or Brescia) | ||
| TYPE OF BETA-THAL | beta° | ||
| MECHANISM | This mutation results in the formation of an unstable betaX chain which is rapidly catabolized causing beta-thal | ||
| IDENTIFICATION | Amplification of the beta-globin gene; DNA sequencing; the mutation creates an MspI site which is used for identification | ||
| HEMATOLOGY IN HETEROZYGOTE(S) | Proband has splenomegaly; no inclusion bodies; marked erythroid hyperplasia in the bone marrow; Hb 8.6, 9.5 g/dl; MCV 72 fl; Hb F 6.1, 7.5%; Hb A2 3.3% | ||
| HEMATOLOGY IN HOMOZYGOTE(S) | None observed | ||
| OCCURRENCE | A 29-year-old Caucasian female from North Carolina, USA; family history of anemia (perhaps six additional cases); also in an Italian and two Russian families | ||
| HAPLOTYPE | Not determined | ||
| FOUND IN COMBINATION WITH ABNORMAL HB(S) | Not reported | ||
| FOUND IN COMBINATION WITH BETA-THAL ALLELE(S) | Not reported | ||
| OTHER INFORMATION | Computer generated images of the G helix suggest that amino acid substitutions with side chains projecting into the heme pocket may destabilize heme resulting in a beta-thal phenotype (decreased alpha1beta1 interactions); there are several exon 3 mutants falling into this category |
| REFERENCES | |||
| 1. | DeCastro, C.M., Devlin, B., Fleenor, D.E., Lee, M.E., and Kaufman, R.E.: Blood, 83:1109, 1994. | ||
| 2. | Murru, S.: Personal communication, 1992. | ||
| 3. | Çürük, M.A., Molchanova, T.P., Postnikov, Yu.V., Pobedimskaya, D.D., Liang, R., Baysal, E., Kolodey, S., Smetanina, N.S., Tokarev, Yu.N., Rumyantsev, A.G., and Huisman, T.H.J.: Am. J. Hematol., 46:329, 1994. | ||