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| MUTATION | |
TAA->CAA at codon 142 of the alpha2 gene | |
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| AMINO ACID REPLACEMENT | |
Stop codon->Gln +30 additional amino acids (Hb Constant Spring) | |
| TYPE OF ALPHA-THAL | |
alpha-Thal-2 [alpha(T)alpha/alphaalpha] | |
| MECHANISM | |
This T->C mutation results in an extension of the alpha chain with 31 amino acid residues; a stop codon is found at the new codon 173 | |
| IDENTIFICATION | |
Originally by protein analysis; in later times by amplification of the alpha2-globin gene and DNA sequencing; dot-blot analysis with allele specific probes; ASO | |
| HEMATOLOGY IN HETEROZYGOTE(S) | |
Hb 10.0-13.5 g/dl; MCV 61-87 fl; MCH 17-27 pg; Hb A2 2.4-3.1% | |
| HEMATOLOGY IN HOMOZYGOTE(S) | |
Hb 11-12 g/dl; MCV 73-75 fl; MCH 21-24 pg; Hb A2 1.8-2.0% | |
| OCCURRENCE | |
Rather widespread in East Asian populations; mainly Chinese; incidence in Bangkok 1.5% | |
| HAPLOTYPE | |
Not determined | |
| FOUND IN COMBINATION | |
With Hb E | |
| FOUND IN COMBINATION | |
With different alpha-thal alleles: | |
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| - -(SEA)/alpha(CS)alpha | = Hb H disease; | | -alpha(3.7)/alpha(CS)alpha | = alpha-thal-1 type of condition; | | -alpha(4.2)/alpha(CS)alpha | = same |
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| OTHER INFORMATION | |
Hb CS is present for >2% in the heterozygote and >5% in homozygotes; the protein is unstable | |
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| REFERENCES |
| 1. | |
Milner, P.F., Clegg, J.B., and Weatherall, D.J.: The Lancet, i:729, 1971. | |
| 2. | |
Clegg, J.B., Weatherall, D.J., and Milner, P.F.: Nature, 234:337, 1971. | |
| 3. | |
Efremov, G.D., Wrightstone, R.N., Huisman, T.H.J., Schroeder, W.A., Hyman, C., Ortega, J., and Williams, K.: J. Clin. Invest., 50:1628, 1971. | |
| 4. | |
Lie-Injo, L.E., Ganesan, J., Clegg, J.B., and Weatherall, D.J.: Blood, 43:251, 1974. | |
| 5. | |
Thonglairoam, V., Winichagoon, P., Fucharoen, S., Tanphaichitr, V.C., Pung-amritt, P., Embury, S.H., and Wasi, P.: Am. J. Hematol., 38:277, 1991. | |
| 6. | |
Xu, X-M., Zhang, J-Z., and Li, S-K.: Hemoglobin, 18:61, 1994. | |