Thalassemia Intermedia As A Result Of Heterozygosis For β0-thalassemia And αααanti-3.7/αα Genotype In A Brazilian Patient

We report a case in which the interaction of heterozygosis for both the β0-IVS-II-1 (G→A) mutation and the αααanti-3.7 allele was the probable cause for the clinical occurrence of thalassemia intermedia. The propositus, a 6-year-old Caucasian Brazilian boy of Portuguese descent, showed a moderately severe chronic anemia in spite of having the β-thalassemia trait. Investigation of the α-globin gene status revealed heterozygosis for α-gene triplication (ααα/αα). The patient's father, also presenting mild microcytic and hypochromic anemia, had the same α and β genotypes as his son, while the mother, not related to the father and hematologically normal, was also a carrier of the αααanti-3.7 allele. The present case emphasizes the need for considering the possibility of α-gene triplication in β-thalassemia heterozygotes who display an unexpected severe phenotype. The β-thalassemia mutation found here is being described for the first time in Brazil.366699701Traeger-Synodinos, J., Kanavakis, E., Vrettou, C., Maragoudaki, E., Nichael, T., Metaxotou-Mavromati, A., Kattamis, C., The triplicated α-globin gene locus in β-thalassaemia heterozygotes: Clinical, haematological, biosynthetic and molecular studies (1996) British Journal of Haematology, 95, pp. 467-471Camaschella, C., Kattamis, A.C., Petroni, D., Different hematological phenotypes caused by the interaction of triplicated α-globin genes and heterozygous β-thalassemia (1997) American Journal of Hematology, 55, pp. 83-88Weatherall, D.J., Clegg, J.B., (1981) The Thalassaemia Syndromes, , 3rd edn. Blackwell Scientific Publications, OxfordPembrey, M.E., MacWade, P., Weatherall, D.J., Reliable routine estimation of small amounts of foetal haemoglobin by alkali denaturation (1972) Journal of Clinical Pathology, 25, pp. 738-740Miranda, S.R.P., Fonseca, S.F., Figueiredo, M.S., Grotto, H.Z.W., Kimura, E.M., Saad, S.T.O., Costa, F.F., Hb Köln [α2β298(FG5) Val→Met] identified by DNA analysis in a Brazilian family (1997) Brazilian Journal of Genetics, 20, pp. 745-748Dodé, C., Rajagopal, K., Lamb, J., Rochette, J., Rapid analysis of -α3.7 thalassaemia and αααanti3.7 triplication by enzymatic amplification analysis (1993) British Journal of Haematology, 82, pp. 105-111Huisman, T.H.J., Carver, M.F.H., Baysal, E., (1997) A Syllabus of Thalassemia Mutations, , The Sickle Cell Anemia Foundation, Augusta, USAColah, R.B., Nadkarni, A.H., Mukherjee, M.B., Gorakshakar, A.C., Surve, R., Mohanty, D., β-Thalassaemia heterozygotes with α-globin gene triplication (1997) British Journal of Haematology, 97, pp. 506-507Ho, P.J., Hall, G.W., Luo, L.Y., Weatherall, D.J., Thein SL Beta thalassaemia intermedia: Is it possible consistently to predict phenotype from genotype? (1998) British Journal of Haematology, 100, pp. 70-78Ma, S.K., Au, W.Y., Chan, A.Y., Chan, L.C., Clinical phenotype of triplicated alpha-globin genes and heterozygosity for β0-thalassemia in Chinese subjects (2001) International Journal of Molecular Medicine, 8, pp. 171-175Sampietro, M., Cazzola, M., Cappellini, M.D., Fiorelli, G., The triplicated alpha-gene locus and heterozygous β-thalassaemia: A case of thalassaemia intermedia (1983) British Journal of Haematology, 55, pp. 709-710Beris, P., Darbellay, R., Hochmann, A., Pradervand, E., Pugin, P., Interaction of heterozygous β0-thalassemia and triplicated α-globin loci in a Swiss-Spanish family (1991) Klinische Wochenschrift, 69, pp. 710-714Oron, V., Filon, D., Oppenhein, A., Rund, D., Severe thalassemia intermedia caused by interaction of homozygosity for α-globin gene triplication with heterozygosity for β0-thalassemia (1994) British Journal of Haematology, 86, pp. 377-379Rund, D., Oron-Karni, V., Filon, D., Goldfarb, A., Rachmilewitz, E., Oppenheim, A., Genetic analysis of β-thalassemia intermedia in Israel: Diversity of mechanisms and unpredictability of phenotype (1997) American Journal of Hematology, 54, pp. 16-22Zeng, Y., Huang, S., The studies of hemoglobinopathies and thalassemia in China - The experiences in Shangai Institute of Medical Genetics (2001) Clinica Chimica Acta, 313, pp. 107-111Galanello, R., Ruggeri, R., Paglietti, E., Addis, M., Melis, M.A., Cao, A., A family with segregating triplicated alpha-globin loci and beta-thalassemia (1983) Blood, 62, pp. 1035-1040Kanavakis, E., Metaxotou-Mavromati, A., Kattamis, C., Wainscoat, J.S., Wood, W.G., The triplicated alpha gene locus and beta thalassemia (1983) British Journal of Haematology, 54, pp. 201-20