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Hb Köln [α2fβ298(FG5) vai-met] identified by DNA analysis in a Brazilian family
Silvia R.P. MirandaI; Silvana F. FonsecaII; Maria S. FigueiredoII; Myoko YamamotoII; Helena Z.W. GrottoI; Sara T.O. SaadI; Fernando F. CostaI
IDepartamento de Clínica Médica and Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Caixa Postal 6111, 13083-970 Campinas, SP, Brasil. Phone: (019) 239-7866; Fax: (019) 239-3114. E-mail: fcmadm@turing.unicamp.br. Send correspondence to F.F.C.
IIDepartamento de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
ABSTRACT
Hb Köln was identified by DNA analysis in a Brazilian patient. A four-year old Brazilian female, with jaundice since birth, presented an abnormal band, between A2 and S, in hemoglobin electrophoresis on a cellulose acetate membrane, and a band with electrophoretic migration similar to Hb C on agar gel. Thermic instability and isopropanol precipitation tests were positive. Heinz bodies were observed in the patient's peripheral blood. Sequencing of the three exons of the β globin gene detected a transition from G to A in the first position of codon 98. This alteration does not create or abolish any known restriction site. In this case, confirmation of the mutation was accomplished by allele-specific oligonucleotide hybridization, which is a simple and fast identification method when the clinical data and hematological and electrophoretic patterns are suggestive of Hb Köln.
Keywords: Hb Köln; DNA analysis.
REFERENCES
Carrell, R.W., Lehmann, H. and Hutchison, H.E. (1966). Haemoglobin Köln (13 98 Valine-Methionine): an unstable protein causing inclusion body anaemia. Nature 210: 915-916.
Dacie, J.V. and Lewis, S.M. (1984). Practical Haematology. Churchill Livingstone, Edinburg, New York.
Eisenger, J., Flores, J., Tyson, J.A. and Shohet, S.B. (1985). Fluorescent cytoplasm and Heinz bodies of hemoglobin Köln erythrocytes: evidence for intracellular heme catabolism. Blood 65: 886-893.
Fairbanks, V.F., Opfell, R.W. and Burgert Jr., E.O. (1969). Three families with unstable hemoglobinopathies (Köln, Olmsted and Santa Ana) causing hemolytic anemia with inclusion bodies and pigmenturia. Am. J. Med. 46: 344-359.
Harley, J.D. and Mauer, A.M. (1961). Studies on the formation of Heinz bodies. II. The nature and significance of Heinz bodies. Blood 17: 418-433.
Lolskin, G.B. and Miller, D.R. (1976). Heme synthesis in hereditary hemolytic anemias: decrease of 8-aminolevulinic synthetase in hemoglobin Köln disease. Pediat. Res. 10: 702-706.
Marengo-Rowe, A.J. (1965). Rapid electrophoresis and quantitation of haemoglobin on cellulose acetate. J. Clin. Pathol. 18: 790-792.
Miller, D.R., Weed, R.I., Stamatoyannopoulos, G. and Yoshida, A. (1971). Hemoglobin Köln disease occurring as a fresh mutation erythrocyte metabolism and sur- vival. Blood 38: 715-729.
Naoum, P.C., Domingos, C.R.B., Moreira, H.W. and Alvares Fo., F. (1993a). Hb Köln or β2132 98 (FG5) Val-Met in Brazil. 5th International Conference on Thalassemias and the Haemoglobinopathies. Nicosia, Cyprus.
Naoum, P.C., Domingos, C.R.B., Moreira, H.W. and Alvares Fo., F. (1993b). Hb Köln or a213298 (FG5) Val-Met in Brazil. Simpósio Nacional de Hemoglobinopatias. São José do Rio Preto, SP, Brasil.
Pedersen, P.R., McCurdy, P.R., Wrightstone, R.N., Wilson, J.B., Smith, L.L. and Huisman, T.H.J. (1973). Hemoglobin Köln in a black: pre- and post-splenectomy red cell survival (DF32P and 51Cr) and the pathogenesis of hemoglobin instability. Blood 42: 771-781.
Pembrey, M.E., MacWade, P. and Weatherall, D.J. (1972). Reliable routine stimulation of small amounts of foetal hemoglobin by alkali denaturation. J. Clin. Pathol. 25: 738-740.
Sambrook, J., Fritsch, E.F. and Maniatis, T. (1989). Molecular Cloning. Cold Spring Harbor Laboratories, New York.
Scott, J.L., Haut, A., Cartwright, G.E. and Wintrobe, M.M. (1960). Congenital hemolytic disease associated with red cell inclusion bodies, abnormal pigment metabolism and electrophoretic hemoglobin abnormality. Blood 16: 1239-1252.
Vaughan Jones, R., Grimes, A.J., Carrel, R.W. and Lehman, H. (1967). Köln haemoglobinopathy: further data and a comparison with other hereditary Heinz bodies anaemias. Brit. J. Haematol. 13: 394-408.