A C→T substitution at nt -101 in a conserved DNA sequence of the promotor region of the β-globin gene is associated with 'silent' β-thalassemia

J. M. Gonzalez-Redondo, T. A. Stoming, A. Kutlar, F. Kutlar, K. D. Lanclos, E. F. Howard, Y. J. Fei, M. Aksoy, C. Altay, A. Gurgey, A. N. Basak, G. D. Efremov, G. Petkov, T. H.J. Huisman

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111 Scopus citations

Abstract

Sequence analyses and dot-blot analyses with synthetic oligonucleotide probes have identified eight individuals in three Turkish families and one Bulgarian family with one chromosome having a C→T mutation at nucleotide position -101 relative to the Cap site of the β-globin gene. This nucleotide is part of one of the conserved blocks of nucleotides within the promoter region; in vitro expression analyses with the chloramphenicol acetyltransferase system showed that this substitution will decrease the effectiveness of transcription. Five subjects had a thalassemia intermedia due to the additional presence of a known classical high hemoglobin (Hb) A2 β-thalassemia mutation on the second chromosome; their hematologic condition was relatively mild. The three persons with a heterozygosity for the -101 C→T mutation had normal hematologic data without microcytosis but with high-normal levels of Hb A2 and a mild imbalance in chain synthesis. The newly discovered mutation is considered one of the silent types of β-thalassemia. It is relatively rare because it was absent among several hundred normal and β-thalassemia chromosomes.

Original languageEnglish (US)
Pages (from-to)1705-1711
Number of pages7
JournalBlood
Volume73
Issue number6
StatePublished - Jan 1 1989

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Gonzalez-Redondo, J. M., Stoming, T. A., Kutlar, A., Kutlar, F., Lanclos, K. D., Howard, E. F., Fei, Y. J., Aksoy, M., Altay, C., Gurgey, A., Basak, A. N., Efremov, G. D., Petkov, G., & Huisman, T. H. J. (1989). A C→T substitution at nt -101 in a conserved DNA sequence of the promotor region of the β-globin gene is associated with 'silent' β-thalassemia. Blood, 73(6), 1705-1711.