|
|
|
|
| MUTATION | |
AATAAA->AATAAG of the alpha2 gene (poly A signal) | |
| |
| AMINO ACID REPLACEMENT | |
None | |
| TYPE OF ALPHA-THAL | |
alpha-Thal-2 [alpha(T)alpha/alphaalpha] | |
| MECHANISM | |
This mutation in the poly A signal results in an extended transcript with a new signal 1048 bp 3' to the terminating codon; nonfunctional mRNA | |
| IDENTIFICATION | |
Cloning or amplification of the alpha2-globin gene; DNA se-quencing; dot-blot analysis with allele specific probes; ASO | |
| HEMATOLOGY IN HETEROZYGOTE(S) | |
For hematological and Hb composition data see table from Ref. 4 (below) | |
| |
| Sex-Age | Hb
g/dl | PCV
l/l | RBC
1012/l | MCV
fl | MCH
pg | MCHC
g/dl | A2
% | % H +
Bart's |
| | Homozygotes (n = 7) | F-10
M-14
F-42
F-21
M-16
Adult
M-13 | 7.0
7.0
9.7
9.0
9.9
7.7
8.6 | 0.289
0.295
0.424
0.393
0.421
0.290
0.306 | 3.94
3.90
5.25
4.72
5.14
4.05
4.37 | 73.4
75.6
80.5
83.5
82.0
71.6
70.0 | 17.8
17.9
18.4
19.1
19.3
19.0
19.5 | 24.2
23.7
22.9
23.5
26.6
28.0
28.1 | 0.7
1.4
0.6
0.7
0.7
0.8
1.4 | 14.0
6.5
7.0
20.0
25.0
n.d.
17.0 | | Average | 8.4 | 0.345 | 4.48 | 77.0 | 18.8 | 24.3 | 0.9 | 15.0 |
| | Heterozygotes (n = 10) | F-adult
M-adult
F-adult
M-adult
M-adult
M-adult
M-adult
M-adult
F-adult
F-adult | 12.6
12.6
10.9
13.3
10.8
16.4
15.2
13.5
14.6
11.9 | 0.459
0.460
0.377
0.465
0.381
0.560
0.476
0.418
0.451
0.352 | 5.12
5.15
4.37
5.22
4.64
6.60
5.80
5.10
5.50
4.60 | 89.6
89.3
86.3
89.1
82.1
84.3
82.1
82.0
82.0
77.0 | 24.6
24.5
24.9
25.5
23.3
24.7
26.2
26.5
26.5
25.8 | 27.5
27.4
28.9
28.6
28.3
29.3
31.9
32.3
32.1
33.8 | 2.2
2.5
2.4
2.5
2.4
2.2
2.1
2.4
2.7
2.8 | 0
0
0
0
0
0
0
0
0
0 | | Average | 13.2 | 0.440 | 5.21 | 84.5 | 25.3 | 30.0 | 2.4 | 0 |
| | |
| HEMATOLOGY IN HOMOZYGOTE(S) | |
Homozygosity expresses as Hb H disease probably because the presence of an extended transcript reduces the expression of the 3' alpha1-globin gene | |
| OCCURRENCE | |
In Arabian populations | |
| HAPLOTYPE | |
Not determined | |
| FOUND IN COMBINATION WITH ABNORMAL HB(S) | |
Not reported | |
| FOUND IN COMBINATION | |
With different alpha-thal alleles (deletional and nondeletional mutations) | |
| OTHER INFORMATION | |
None | |
|
|
|
|
| REFERENCES |
| 1. | |
Higgs, D.R., Goodbourn, S.E.Y., Lamb, J., Clegg, J.B., Weatherall, D.J., and Proudfoot, N.J.: Nature, 306:398, 1983. | |
| 2. | |
Thein, S.L., Wallace, R.B., Pressley, L., Clegg, J.B., Weatherall, D.J., and Higgs, D.R.: Blood, 71:313, 1988. | |
| 3. | |
Whitelaw, E. and Proudfoot, N.: EMBO J., 5:2915, 1986. | |
| 4. | |
Fei, Y-J., Oner, R., Bozkurt, G., Gu, L-H., Altay, Ç., Gurgey, A., Fattoum, S., Baysal, E., and Huisman, T.H.J.: Acta Haematol., 88:82, 1992. | |
| 5. | |
Adekile, A.D., Gu, L-H., Baysal, E., Haider, M.Z., Al-Fuzae, L., Aboobacker, K.C., Al-Rashied, A., and Huisman, T.H.J.: Acta Haematol., 92:176, 1994. | |