Association in cis of β+‐thalassemia and hemoglobin S

A Moroccan woman was investigated because of a typical β‐thalassemia trait associated with a low‐percentage (11%) hemoglobin (Hb) variant. The β‐thalassemia trait was manifested by a microcytosis, a high HbA2 (above 6%), and an increase of the α/β biosynthetic ratio (1.31). The variant was identified to HbS by amino acid analysis of the abnormal peptide (β T1) and by DNA mapping with Sau I (Mst II) restriction endonuclease. No additional amino acid substitution was recorded in the βs‐chain. The reduction of β‐globin synthesis occurred exclusively at the expense of the βs‐chain. These results are consistent with the existence of a βs mutation and a β+‐thalassemia in cis.

[1]  M. Vidaud,et al.  Hemoglobin S Antilles: a variant with lower solubility than hemoglobin S and producing sickle cell disease in heterozygotes. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[2]  A. Kutlar,et al.  Sickle cell anaemia among Eti‐Turks: haematological, clinical and genetic observations , 1986, British journal of haematology.

[3]  J. Delaunay,et al.  Homozygous hemoglobin Knossos (alpha 2 beta 227(B9) Ala----Ser): a new variety of beta+-thalassemia intermedia associated with delta degree- thalassemia , 1986 .

[4]  N. Anagnou,et al.  A new gene deletion in the alpha-like globin gene cluster as the molecular basis for the rare alpha-thalassemia-1(--/alpha alpha) in blacks: HbH disease in sickle cell trait. , 1986, Blood.

[5]  D. Loukopoulos,et al.  Hemoglobin knossos: A clinical, laboratory, and epidemiological study , 1986, American journal of hematology.

[6]  A. Di Rienzo,et al.  Association of Hb H disease with sickle-trait. , 1986, Hemoglobin.

[7]  S. Orkin,et al.  Abnormal processing of beta Knossos RNA , 1984 .

[8]  T. Huisman,et al.  The rare alpha-thalassemia-1 of blacks is a zeta alpha-thalassemia-1 associated with deletion of all alpha- and zeta-globin genes , 1984 .

[9]  D. Labie,et al.  Evidence for the multicentric origin of the sickle cell hemoglobin gene in Africa. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[10]  S. Antonarakis,et al.  Origin of the beta S-globin gene in blacks: the contribution of recurrent mutation or gene conversion or both. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[11]  J. Clegg,et al.  Association of two DNA polymorphisms in the alpha-globin gene cluster: implications for genetic analysis. , 1983, American journal of human genetics.

[12]  N. Robert,et al.  In Waldenstrom's macroglobulinemia the quantity of detectable circulating monoclonal B lymphocytes correlates with clinical course. , 1983, Blood.

[13]  B. Hedlund,et al.  Hemoglobin North Shore: a variant hemoglobin associated with the phenotype of beta-thalassemia. , 1983, Blood.

[14]  Stylianos E. Antonarakis,et al.  Abnormal RNA processing due to the exon mutation of βE-globin gene , 1982, Nature.

[15]  A. Francina,et al.  Microchromatofocusing of hemoglobins. Increased hemoglobin A2 percentage in sickle cell trait. , 1982, Clinica chimica acta; international journal of clinical chemistry.

[16]  D. Labie,et al.  The sickle gene polymorphism in North Africa. , 1981, Blood.

[17]  E. Benz,et al.  beta-Thalassemia present in cis to a new beta-chain structural variant, Hb Vicksburg [beta 75 (E19)Leu leads to 0]. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[18]  W. J. Whitten,et al.  The proportion of Hb A2 is higher in sickle cell trait than in normal homozygotes. , 1981, Hemoglobin.

[19]  J. Clegg,et al.  Defective synthesis of HbE is due to reduced levels of βE mRNA , 1980, Nature.

[20]  Y. Kan,et al.  Two different molecular organizations account for the single alpha-globin gene of the alpha-thalassemia-2 genotype. , 1980, The Journal of clinical investigation.

[21]  B. Alter,et al.  Globin Chain Electrophoresis: a New Approach to the Determination of the Gγ/Aγ Ratio in Fetal Haemoglobin and to Studies of Globin Synthesis , 1980 .

[22]  Y. Kan,et al.  Modification of hemoglobin H disease by sickle trait. , 1979, The Journal of clinical investigation.

[23]  L. Boxer,et al.  Hemoglobin Indianapolis (beta 112[G14] arginine). An unstable beta-chain variant producing the phenotype of severe beta-thalassemia. , 1979, The Journal of clinical investigation.

[24]  Y. Kan,et al.  Polymorphism of DNA sequence adjacent to human beta-globin structural gene: relationship to sickle mutation. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[25]  P. Basset,et al.  Isoelectric focusing of human hemoglobin: its application to screening, to the characterization of 70 variants, and to the study of modified fractions of normal hemoglobins. , 1978, Blood.

[26]  A. Jeffreys,et al.  A physical map of the DNA regions flanking the rabbit β-globin gene , 1977, Cell.

[27]  R. Nagel,et al.  Hemoglobin S Travis: a Sickling Hemoglobin with Two Amino Acid Substitutions [β6(A3)Glutamic Acid → Valine and β 142(H20) Alanine → Valine] , 1977 .

[28]  T. Huisman.  Trimodality in Tie Percentages of β Chain Variants in Heterozy-Gotes: The Effect of the Number of Aczive HBα Structural Loci , 1977 .

[29]  E. Southern.  Detection of specific sequences among DNA fragments separated by gel electrophoresis. , 1975, Journal of molecular biology.

[30]  P. Basset,et al.  Hemoglobin C Ziguinchor αA 2β6 2 (A3)Glu → Val β58(E2)→ Arg: The second sickling variant with amino acid substitutions in 2 residues of the β polypeptide chain , 1975 .

[31]  M. Steinberg,et al.  Alpha Thalassaemia in Adults with Sickle‐Cell Trait , 1975, British journal of haematology.

[32]  P. Milner,et al.  The clinical features of sickle-cell- thalassaemia in Jamaica. , 1973, British journal of haematology.

[33]  R. Nagel,et al.  Structure and Properties of Hemoglobin Charlem, a Human Hemoglobin Variant with Amino Acid Substitutions in 2 Residues of the β-Polypeptide Chain , 1967 .

[34]  J. Clegg,et al.  Abnormal human haemoglobins , 1966 .

[35]  J. Lingrel,et al.  A Comparison of Amino Acid Incorporation into the Hemoglobin and Ribosomes of Marrow Erythroid Cells and Circulating Reticulocytes of Severely Anemic Rabbits , 1963 .

[36]  K. Betke,et al.  Estimation of Small Percentages of Fœtal Hæmoglobin , 1959, Nature.

[37]  H. Itano.  Solubilities of naturally occurring mixtures of human hemoglobin. , 1953, Archives of biochemistry and biophysics.