| MUTATION | G->C at codon 130 of the alpha2 gene; GCT->CCT | ||
|---|---|---|---|
| AMINO ACID REPLACEMENT | Ala->Pro at position 130 (Hb Sun Prairie) | ||
| TYPE OF ALPHA-THAL | alpha-Thal-2 [alpha(T)alpha/alphaalpha] | ||
| MECHANISM | The G->C mutation results in an unstable Hb and a decreased level of alpha chains | ||
| IDENTIFICATION | Gene mapping; amplification of the alpha2 globin gene; sequencing; dot-blot analysis with mutation specific probes | ||
| HEMATOLOGY IN HETEROZYGOTE(S) | Hb 10.8-14.7 g/dl; microcytosis and hypochromia; MCV ~75 fl; MCH ~24 pg | ||
| HEMATOLOGY IN HOMOZYGOTE(S) | The proband was adopted, so family studies were not possible; he is considered a homozygote: Hb 9.8 g/dl; MCV 60 fl; MCH 18 pg; reticulocytes 6.5%; moderate splenomegaly; Heinz bodies were positive. Two homozygotes with a somewhat similar phenotype have been found in a Pakistani family; alpha/beta ratio 2.7-2.9 | ||
| OCCURRENCE | In a few Indian and Pakistani 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 | A small amount of the unstable Hb could be detected by heat stability and by HPLC (~2.5%); the Ala->Pro replacement was detected in a tryptic digest of the alphaX chain, isolated by reversed phase HPLC |
| REFERENCES | |||
| 1. | Harkness, M., Harkness, D.R., Kutlar, F., Kutlar, A., Wilson, J.B., Webber, B.B., Codrington, J.F., and Huisman, T.H.J.: Hemoglobin, 14:479, 1990. | ||
| 2. | Plaseska, D., Gu, L-H., Wilson, J.B., Codrington, J.F., Huisman, T.H.J., and Dash, S.: Hemoglobin, 14:491, 1990. | ||
| 3. | Ho, P.J., Rochette, J., Rees, D.C., Fisher, C.A., Huehns, E.R., Will, A.M., and Thein, S.L.: Hemoglobin, 20:103, 1996. | ||