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MUTATION | |
-117 (G->A) Agamma; the Greek-Italian nd-HPFH | |
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IDENTIFICATION | |
Cloning and amplification; DNA sequencing | |
HEMATOLOGY IN HETEROZYGOTE(S) | |
Normal; Hb F 13.6 (7.1-19.0)% (n=42); Ggamma 5.0%;Hb A2 2.05 (1.2-3.0)% (n=37) | |
HEMATOLOGY IN HOMOZYGOTE(S) | |
Hb F 24.0; 24.0%; Hb A2 0.8; 0.8% | |
OCCURRENCE | |
In Greek and Italian families | |
HAPLOTYPE | |
Type VII [+ - - - - - +] | |
FOUND IN COMBINATION WITH ABNORMAL HB(S) | |
None reported | |
FOUND IN COMBINATION WITH BETA-THAL ALLELE(S) | |
With an undefined beta-thal allele: Hb A2 4.2%; Hb F 41.8% | |
MECHANISM | |
This mutation occurs in a CCAAT element; three proteins can bind here: the ubiquitous CpI; the erythroid cell-specific NF-E, and a third, less well-defined, protein. This mutation likely alters the binding of one or more of these factors | |
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REFERENCES |
1. | |
Fessas, Ph. and Stamatoyannopoulos, G.: Blood, 24:223, 1964. | |
2. | |
Sofroniadou, K., Wood, W.G., Nute, P.E., and Stamatoyannopoulos, G.: Br. J. Haematol., 29:137, 1975. | |
3. | |
Collins, F.S., Metherall, J.E., Yamakawa, M., Pan, J., Weissman, S.M., and Forget, B.G.: Nature, 313: 325, 1985. | |
4. | |
Gelinas, R., Endlich, B., Pfeiffer, C., Yagi, M., and Stamatoyannopoulos, G.: Nature, 313:323, 1985. | |
5. | |
Superti-Furga, G., Barberis, A., Schaffner, G., and Busslinger, M.: EMBO J., 7:3099, 1988. | |
6. | |
Ottolenghi, S., Camaschella, C., Comi, P., Giglioni, B., Longinotti, M., Oggiano, L., Dore, F., Sciarratta, G., Ivaldi, G., Saglio, G., Serra, A., Loi, A., and Pirastu, M.: Hum. Genet., 79:13, 1988. | |
7. | |
Camaschella, C., Oggiano, L., Sampietro, M., Gottardi, E., Alfarano, A., Pistidda, P., Dore, F., Taramelli, R., Ottolenghi, S., and Longinotti, M.: Blood, 73:1999, 1989. | |