Summary
A new abnormal heat labile haemoglobin causing marked Heinz body anaemia is reported. This haemoglobin, which was found in a German family, was shown to be abnormal in the non-alpha-polypeptide chain.
After separation and purification of the non-alpha polypeptide chain further investigations by thin layer “finger-printing” on silicagel starch and amino acid analysis have shown multiple aberration in the amino acid sequence of the abnormal polypeptide chain. Therefore, this abnormality cannot be caused by exchange of one amino acid. Most probably Hb Frankfurt is the result of a “crossover”—Lepore-Hb—or of a deletion (or insertion) of one or two nucleotides on the DNA or RNA chains, respectively.
Zusammenfassung
In einer deutschen Sippe wurde ein anomales Hämoglobin gefunden, das bei den Betroffenen eine Heinz-Körper-Anämie verursacht. Es handelt sich um ein hitzelabiles Hämoglobin.
Die Anomalie dieses instabilen Hb ist in der Nicht-α-Kette lokalisiert.
Die Polypeptidketten dieses Hb wurden mittels Ionenaustauscher-Chromatographie voneinander getrennt. Nach anschließender Reinigung durch Gel-Filtration wurde die Nicht-α-Kette mit Hilfe des Fingerprintverfahrens und der quantitativen Aminosäuren-Analyse weiter untersucht. Es fanden sich multiple Abweichungen in der Aminosäurenzusammensetzung. Danach kann die Anomalität nicht wie bei den bislang bekannt gewordenen anomalen Hämoglobinen durcheinen Aminosäurenaustausch verursacht sein.
Hb Frankfurt ist wahrscheinlich das Ergebnis eines „crossover“-Lepore-Hb- oder einer Deletion bzw. Insertion von ein oder zwei Nukleotiden auf der DNS- bzw. RNS-Kette.
Similar content being viewed by others
Literatur
Baglioni, C.: An improved method for the fingerprinting of human hemoglobin. Biochim. biophys. Acta (Amst.)48, 392 (1961).
Baglioni, C.: The fusion of two peptide chains in hemoglobin Lepore and its interpretation as a genetic deletion. Proc. nat. Acad. Sci. (Wash.)48, 1880 (1962).
Baglioni, C.: The fusion of two genes in carriers of hemoglobin Lepore. Atti Assoc. genet. ital. Roma8, 86 (1963).
Baglioni, C.: The chemical structure of hemoglobin Lepore and its interpretation as the result of non-homologous crossing-over. Genetics today, vol. 1, p. 294. Proc. XI. Int. Congr. Genet. The Hague, The Netherlands, Sept. 1963. Oxford-London-New York-Paris: Pergamon Press 1963.
Barkhan, P., Stevenson, M.E., Pinker, G.: Haemoglobin Lepore trait. An analysis of the abnormal haemoglobin. Brit. J. Haemat.10, 437 (1964).
Barnabas, J., Müller, C.J.: Haemoglobin-Lepore (Hollandia). Nature (Lond.)194, 931 (1962).
Beaven, G.H., Gratzer, W.B., Stevens, B.L., Shooter, E.M., Ellis, M.J., White, J.C., Gillespie, J.E.O'N.: An abnormal haemoglobin (Lepore/Cyprus) resembling haemoglobin-Lepore and its interaction with thalassaemia. Brit. J. Haemat.10, 159 (1964).
Boyer, S.H., Rucknagel, D.L., Weatherall, D.J., Watson-Williams, E. J.: Further evidence for linkage between the β and δ loci governing human hemoglobin and the population dynamics of linked genes. Amer. J. hum. Genet.15, 438 (1963).
Braun, V., Crichton, R.R., Braunitzer, G.: Hämoglobine, XV. Über monomere und dimere Insektenhämoglobine (Chironomus thummi). Hoppe-Seylers Z. physiol. Chem.349, 197 (1968).
Braunitzer, G.: Die Primärstruktur der Eiweißstoffe. Naturwissenschaften54, 407 (1967).
Braunitzer, G., Buse, G., Braig, S.: Über die Konstanz der monomeren und dimeren Hämoglobine (Erythrocruorine) der Mücke Chironomus thummi. Hoppe-Seylers Z. physiol. Chem.349, 263 (1968).
Carrell, R.W., Irvine, D.: Characterization of the α chain core of human haemoglobins variants. Biochim. biophys. Acta (Amst.)154, 78 (1968).
Chernoff, A.I., Pettit, N.M., Jr.: The amino acid composition of hemoglobin. III. A qualitative method for identifying abnormalities of the polypeptide chains of hemoglobin. Blood24, 750 (1964).
Curtain, C.C.: A structural study of abnormal haemoglobins occurring in New Guinea. Aust. J. exp. Biol.42 89 (1964).
Eddison, G.G., Briehl, R.W., Ranney, H.M.: Oxygen equilibria of hemoglobin A2 and hemoglobin Lepore. J. clin. Invest.43, 2323 (1964).
Fessas, Ph.: The beta-chain thalassaemias. In: Lehmann und Betke, Haemoglobin-Colloquium, Wien 1961, p. 90. Stuttgart: Thieme 1962.
Fessas, Ph., Stamatoyannopoulos, G., Karaklis, A.: Hemoglobin „Pylos“: Study of a hemoglobinopathy resembling thalassemia in the heterozygous, homozygous and double heterozygous state. Blood19, 1 (1962).
Field, E.O., O'Brien, J.R.P.: Dissociation of human haemoglobin at low pH. Biochem. J.60, 656 (1955).
Gerald, P.S., Diamond, L.K.: A new herediatary hemoglobinopathy (the Lepore trait) and its interaction with thalassemia trait. Blood13, 835 (1958).
Gerald, P.S., Efron, M.L., Diamond, L.K.: A human mutation (the Lepore hemoglobinopathy) possibly involving two “cistrons”. Amer. J. Dis. Child.102, 514 (1961).
Goodwin, T.W., Morton, R.A.: The spectrophotometric determination of tyrosine and tryptophan in proteins. Biochem. J.40, 628 (1946).
Guidotti, G., Hill, R.J., Konigsberg, W.: The structure of human hemoglobin. II. The separation and amino acid composition of the tryptic peptides from the α and β chains. J. biol. Chem.237, 2184 (1962).
Hamilton, P.B.: Ion exchange chromatography of amino acids. Study of effects of high pressures and fast flow rates. Analyt. Chem.32, 1779 (1960).
Hamilton, P.B.: Ion exchange chromatography of amino acids. Microdetermination of free amino acids in serum. N. Y. Acad. Sci.102, 55 (1962).
Hamilton, P.B., Anderson, R.A.: Ion exchange chromatography of amino acids. Semiautomatic method of operation with cationic exchange resin columns. Analyt. Chem.31, 1504 (1959).
Hamilton, P.B., Bogue, D.C., Anderson, R.A.: Ion exchange chromatography of amino acids. Analysis of diffusion (mass transfer) mechanisms. Analyt. Chem.32, 1782 (1960).
Hill, R.J., Konigsberg, W.: The isolation of peptides from tryptic digest of the α-chain from human hemoglobin. J. biol. Chem.235, 21 (1960).
Hilschmann, N., Braunitzer, G.: Über Hämoglobine. XII. Die Sequenzanalyse des Humanhämoglobins. Die Analyse des β-Core-Peptids und des Peptids α Tp 6. Hoppe-Seylers Z. physiol. Chem.335, 21 (1963).
Hobom, G., Braunitzer, G.: Über Hämoglobine. XI. Die Sequenzanalyse des Humanhämoglobins. Die Analyse des α-Core-Peptids. Hoppe-Seylers Z. physiol. Chem.335, 1 (1963).
Holy, H.: Neue Wege in der Säulenchromatographie. Vortrag anl. einer Demonstrationsreise in Deutschland 1963. Sonderdruck Nr. R 154, Technikon GmbH, Frankfurt/Main.
Huisman, T.H.J.: Normal and abnormal human hemoglobins. Advanc. clin. Chem.6, 231 (1963).
Huisman, T.H.J., Dozy, A.M.: Studies on the heterogeneity of hemoglobin. IV. Chromatographic behavior of different human hemoglobins on anion-exchange cellulose (DEAE-Cellulose). J. Chromatog.7, 180 (1962).
Huisman, T.H.J., Dozy, A.M.: Studies on the heterogeneity of hemoglobin IX. The use of Tris (Hydroxymethyl) Aminomethane-HCl buffers in the anion-exchange chromatography of hemoglobins. J. Chromatog.19, 160 (1965).
Hunt, J.A., Ingram, V.M.: Abnormal human haemoglobins. II. The chymotryptic digestion of the trypsinresistant “core” of haemoglobins A and S. Biochim. biophys. Acta (Amst.)28, 546 (1958).
Ingram, V.M.: A specific chemical difference between the globins of normal human and sickle-cell anaemia haemoglobin. Nature (Lond.)178, 792 (1956).
Ingram, V.M.: Gene mutations in human haemoglobin: the chemical difference between normal and sickle-cell haemoglobin. Nature (Lond.)180, 326 (1957).
Ingram, V.M.: Abnormal human haemoglobins. I. The comparison of normal human and sickle-cell haemoglobins by “fingerprinting”. Biochim. biophys. Acta (Amst.)28, 539 (1958).
Ingram, V.M.: Chemistry of the abnormal human haemoglobins. Brit. med. Bull.15, 27 (1959).
Itano, H.A., Robinson, E.: Formation of normal and doubly abnormal haemoglobin by recombination of haemoglobin I with S and C. Nature (Lond.)183, 1799 (1959).
Itano, H.A., Robinson, E.: Properties and inheritance of haemoglobin by asymmetric recombination. Nature (Lond.)184, 1468 (1959).
Itano, H.A., Singer, S.J.: On dissociation and recombination of human adult hemoglobins A, S and C. Proc. nat. Acad. Sci. (Wash.)44, 522 (1958).
Jonxis, J.H.P.: Some remarks on hemoglobinopathies with particular reference to thalassemia. J. Pediat.59, 765 (1961).
Jonxis, J.H.P.: Über Hämoglobinopathien mit besonderer Berücksichtigung der Cooley-Anämie. Schweiz. med. Wschr.91, 1037 (1961).
Jonxis, J.H.P.: A thalassaemia-like picture in a Papuan family. In: Lehmann und Betke, Haemoglobin-Colloquium, Wien 1961, p. 60. Stuttgart: Thieme 1962.
Kraus, L.M.: Formation of different haemoglobins in tissue culture of human bone marrow treated with human doexyribonuelcic adic. Nature (Lond.)192, 1055 (1961).
Lehmann, H., Huntsman, R.G.: Man's haemoglobins. Amsterdam: North-Holland Publ. Comp. 1966.
Lehmann, H., Carrell, R.W.: Variations in the structure of human haemoglobin. With particular reference to the unstable haemoglobins. Brit. med. Bull.25, 14 (1969).
Neeb, H., Beiboer, J.L., Jonxis, J.H.P., Sijpesteijn, J.A.K., Müller, C.J.: Thalassemie met lepore hemoglobine bij twee Papoeakinderen in Nederlands Nieuw-guinea. T. Geneesk.105, 8 (1961).
Neeb, H., Beiboer, J.L., Jonxis, J.H.P., Sijpesteijn, J.A.K., Müller, C.J.: Homozygous Lepore haemoglobin disease appearing as thalassaemia major in two Papuan siblings. Trop. georgr. Med.13, 207 (1961).
Nowicki, L.: Laboratoriumsmethoden zum Nachweis abnormer Hämoglobine. Ärztl. Lab.13, 410 (1967).
Nowicki, L., Martin, H.: Hämoglobin-Fingerprints. Versuche auf Kieselgel-Dünnschichtplatten. Vortrag auf d. 12. Dtsch. Hämatol.-Kongr., Berlin 1966.
Nowicki, L., Martin, H.: Hb Frankfurt: Ein neues instabiles Hämoglobin als Ursache einer Heinzkörperanämie in einer deutschen Sippe. Klin. Wschr.49, 1115 (1971).
Ostertag, W., Smith, E.W.: Hemoglobin-Lepore Baltimore, a third type of aδβ crossover (δ 50,β 86). Europ. J. Biochem.10, 371 (1969).
Pearson, H.A., Gerald, P.S., Diamond, L.K.: Thalassemia intermedia due to interaction of Lepore trait with thalassemia trait. Amer. J. Dis. Child.97, 464 (1959).
Pearson, H.A., McFarland, W.: Erythrokinetics in thalassemia. II. Studies in Lepore trait and hemoglobin H disease. J. Lab. clin. Med.59, 147 (1962).
Perutz, M.F., Lehmann, H.: Molecular pathology of human haemoglobin. Nature (Lond.)219, 902 (1968).
Robinson, E., Itano, H.A.: Identification of the recombinant products of canine and human haemoglobins. Nature (Lond.)188, 798 (1960).
Schram, E., Moore, S., Bigwood, E.J.: Chromatographic determination of cystine as cysteid acid. Biochem. J.57, 33 (1954).
Silvestroni, E., Bianco, I.: Assoziazione di Hb G e microcitemia in due membri di una famiglia italiana del ferrarese. Policlinico, Sez. prat.65, 203 (1958).
Singer, S.J., Itano, H.A.: On the asymmetrical dissociation of human hemoglobin. Proc. nat. Acad. Sci. (Wash.)45, 174 (1959).
Spackman, D.H., Stein, W.H., Moore, S.: Automatic recording apparatus for use in the chromatography of amino acids. Analyt. Chem.30, 1190 (1958).
Stahl, E.: Dünnschicht-Chromaotgraphie. Ein Laboratoriumshandbuch. Berlin-Göttingen-Heidelberg: Springer 1962.
Stamatoyannopoulos, G., Fessas, Ph.: Observations on hemoglobin “Pylos”. The hemoglobin Pylos — hemoglobin S combination. J. Lab. clin. Med.62, 193 (1963).
Sullivan, B., Riggs, A.: The subunit dissociation properties of turtle hemoglobins. Biochim. biophys. Acta (Amst.)140, 274 (1967).
Take, T.: On the dissociation of hemoglobin under the action of urea. J. Biochem. (Tokyo)49, 206 (1961).
Ueda, S.: Agar gel electrophoresis of the hybrid of canine and human hemoglobins: A simple convenient means for the determination of chain anomaly of abnormal hemoglobins. Yamaguchi med. Sch.10, 53 (1963).
Wieland, T., Georgopoulos, D.: Zweidimensionale Auftrennung von Peptiden (Fingerprinttechnik) auf Dünnschichtplatten. Biochem. Z.340, 476 (1964).
Wolf, J.A., Ignatov, V.G.: Heterogeneity of thalassemia major. Amer. J. Dis. Child.105, 234 (1963).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nowicki, L., Martin, H. Hb Frankfurt: Ein neues instabiles Hämoglobin. Klin Wochenschr 50, 454–461 (1972). https://doi.org/10.1007/BF01487600
Issue Date:
DOI: https://doi.org/10.1007/BF01487600